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Sample records for continuous insulin infusion

  1. Insulin Infusion Set: The Achilles Heel of Continuous Subcutaneous Insulin Infusion

    PubMed Central

    Heinemann, Lutz; Krinelke, Lars

    2012-01-01

    Continuous subcutaneous insulin infusion from an insulin pump depends on reliable transfer of the pumped insulin to the subcutaneous insulin depot by means of an insulin infusion set (IIS). Despite their widespread use, the published knowledge about IISs and related issues regarding the impact of placement and wear time on insulin absorption/insulin action is relatively small. We also have to acknowledge that our knowledge is limited with regard to how often patients encounter issues with IISs. Reading pump wearer blogs, for instance, suggests that these are a frequent source of trouble. There are no prospective clinical studies available on current IIS and insulin formulations that provide representative data on the type and frequency of issues with infusion sets. The introduction of new IISs and patch pumps may foster a reassessment of available products and of patient problems related to their use. The aim of this review is to summarize the current knowledge and recommendations about IISs and to highlight potential directions of IIS development in order to make insulin absorption safer and more efficient. PMID:22920824

  2. Nonmetabolic Complications of Continuous Subcutaneous Insulin Infusion: A Patient Survey

    PubMed Central

    Yemane, Nardos; Brackenridge, Anna; Pender, Siobhan

    2014-01-01

    Abstract Background: Little is known about the frequencies and types of nonmetabolic complications occurring in type 1 diabetes patients being treated by modern insulin pump therapy (continuous subcutaneous insulin infusion [CSII]), when recorded by standardized questionnaire rather than clinical experience. Subjects and Methods: A self-report questionnaire was completed by successive subjects with type 1 diabetes attending an insulin pump clinic, and those with a duration of CSII of ≥6 months were selected for analysis (n=92). Questions included pump manufacturer, insulin, infusion set type and duration of use, frequency of infusion set and site problems, pump malfunctions, and patient-related problems such as weight change since starting CSII. Results: Median (range) duration of CSII was 3.3 (0.5–32.0) years, and mean±SD duration of infusion set use was 3.2±0.7 (range 2–6) days. The commonest infusion set problems were kinking (64.1% of subjects) and blockage (54.3%). Blockage was associated with >3 days of use of infusion sets plus lispro insulin in the pump (relative risk [95% confidence interval], 1.71 [1.03–2.85]; P=0.07). The commonest infusion site problem was lipohypertrophy (26.1%), which occurred more often in those with long duration of CSII (4.8 [2.38–9.45] vs. 3.0 [1.50–4.25] years; P=0.01). Pump malfunction had occurred in 48% of subjects (43% in the first year of CSII), with “no delivery,” keypad, and battery problems commonly occurring. Although some patients reported weight gain (34%) and some weight loss (15%) on CSII, most patients (51%) reported no change in weight. Conclusions: Pump, infusion set, and infusion site problems remain common with CSII, even with contemporary technology. PMID:24180294

  3. Safety of continuous subcutaneous insulin infusion: metabolic deterioration and glycaemic autoregulation after deliberate cessation of infusion.

    PubMed

    Pickup, J C; Viberti, G C; Bilous, R W; Keen, H; Alberti, K G; Home, P D; Binder, C

    1982-03-01

    To assess the rate of metabolic deterioration and potential risks of failure of continuous subcutaneous insulin infusion during basal insulin delivery, we deliberately stopped infusion in nine insulin dependent diabetics. Plasma glucose, blood 3-hydroxybutyrate and plasma free insulin were measured for 9 h whilst the patients remained supine and fasting. Mean plasma glucose remained unchanged at normal fasting levels for the first hour, then rose to plateau at about 10 mmol/l until the end of the experiment. The final plateau level of glucose varied from patient to patient; two C-peptide secreting diabetics plateaued at low glucose levels. In contrast, blood 3-hydroxybutyrate rose progressively, without plateauing. PLasma free insulin concentrations fell during the withdrawal period and there was a highly significant negative correlation between free insulin and 3-hydroxybutyrate. No patient was more than mildly unwell after 9 h of insulin deprivation. We conclude that under these experimental conditions there is glycaemic autoregulation and that ketones may sometimes be a more appropriate monitor of insulin deficiency or loss of diabetic control than is glucose. Accidental failure of continuous subcutaneous insulin infusion and interruption of basal delivery in resting and fasting diabetics will probably not cause dangerous metabolic or clinical deterioration.

  4. Circulating insulin antibodies: influence of continuous subcutaneous or intraperitoneal insulin infusion, and impact on glucose control.

    PubMed

    Radermecker, R P; Renard, E; Scheen, A J

    2009-09-01

    The purification of animal insulin preparations and the use of human recombinant insulin have markedly reduced the incidence, but not completely suppressed, the development of anti-insulin antibodies (IAs). Advances in technologies concerning the mode of delivery of insulin, i.e. continuous subcutaneous insulin infusion (CSII), continuous peritoneal insulin infusion (CPII) and more recently inhaled insulin administration, appear to significantly increase circulating levels of immunoglobulin G (IgG) anti-IAs in diabetic patients. However, the increase is usually moderate and mostly transient as compared to previous observations with poorly purified animal insulin preparations. The clinical impact of these circulating anti-IAs remains unclear. Nevertheless, several studies have suggested that antibodies could retard insulin action, leading to a worsening of postprandial hyperglycaemia and/or serve as a carrier, thus leading to unexpected hypoglycaemia. CPII may be associated with more marked and sustained increase in IAs levels, possibly related to the use of an unstable insulin and the formation of immunogenic aggregates of insulin. The possible clinical consequences of these high levels of IAs remain to be evaluated because a low-glucose morning syndrome or severe insulin resistance with ketone bodies production have been reported in some cases. In conclusion, even if CSII and CPII may promote the development of circulating IAs, this increase does not lead to immunological insulin resistance, compared to that previously described with animal non-purified insulin preparations, and seems to have only marginal influence on blood glucose control or complications in most diabetic patients.

  5. Continuous subcutaneous insulin infusion during general anesthesia: a case report.

    PubMed

    White, William A; Montalvo, Helen; Monday, Joshua M

    2004-10-01

    Care of the patient with diabetes mellitus presents numerous challenges to the anesthesia practitioner. There is no perfect way to care for these patients nor are any 2 patients with diabetes exactly alike. With the advent of subcutaneous insulin pumps, the anesthesia practitioner has another tool to assist him or her in giving high quality care. This case study describes the anesthesia care provided to a patient with type 1 diabetes who wore his continuous subcutaneous insulin infusion (CSII) pump during general anesthesia for surgical repair of a herniated lumbar disk. Importantly, the anesthesia plan involved a collaborative effort with the patient. Blood glucose levels were stable throughout the perioperative period. Little or no extra work was required of the CRNA. This case showed that the CSII could be used to minimize perioperative fluctuations in blood sugar. Postoperatively, the patient expressed a high degree of satisfaction with the anesthetic.

  6. Continuous Subcutaneous Insulin Infusion in Patients With Type 2 Diabetes

    PubMed Central

    Megson, Ian L.; Treweeke, Andrew T.; Shaw, Andrew; MacRury, Sandra M.; Setford, Steven; Frias, Juan P.; Anhalt, Henry

    2015-01-01

    Background: Oxidative stress is a detrimental feature of diabetes implicated in the progression of the disease and its complications. The relationship between insulin therapy and oxidative stress is complex. This study tested the hypothesis that improved glucose control, rather than insulin dose, is central to reduced oxidative stress in patients with type 2 diabetes following continuous subcutaneous insulin infusion (CSII). Methods: In this 16-week, multicenter study, 54 CSII-naïve patients with type 2 diabetes (age 57 ± 10 years, HbA1c 69 ± 15 mmol/mol [8.5 ± 1.4%], diabetes duration 13 ± 6 years) treated with either oral antidiabetic agents (OAD) alone (n = 17), basal insulin ± OAD (n = 17), or multiple daily injections (MDI) ± OAD (n = 20) were the evaluable group. Diabetes medications except metformin were discontinued, and 16 weeks of CSII was initiated. Insulin dose was titrated to achieve optimal glycemic control. A plasma marker of oxidative stress relevant to cardiovascular disease (oxidized low density lipoprotein [ox-LDL]) was assessed at baseline and week 16. Results: CSII improved glycemic control (HbA1c −13 ± 2 mmol/mol [−1.2 ± 0.2%]; fasting glucose −36.6 ± 8.4 mg/dL; mean glucose excursion −23.2 ± 6.5 mg/dL, mean ± SE; all P < .001) and reduced ox-LDL (–10.5%; P < .05). The antioxidant effect was cohort-independent (P > .05), but was significantly more pronounced in patients on statins (P = .019). The effect of CSII was more closely correlated to improvements in glucose excursion (P = .013) than to insulin dose (P > .05) or reduction in HbA1c (P > .05). Conclusions: CSII induces depression of plasma ox-LDL associated with change in glucose control, rather than with change in insulin dose. The effect is augmented in patients receiving statins. PMID:25652563

  7. Continuous subcutaneous insulin infusion in Italy: third national survey.

    PubMed

    Bruttomesso, Daniela; Laviola, Luigi; Lepore, Giuseppe; Bonfanti, Riccardo; Bozzetto, Lutgarda; Corsi, Andrea; Di Blasi, Vincenzo; Girelli, Angela; Grassi, Giorgio; Iafusco, Dario; Rabbone, Ivana; Schiaffini, Riccardo

    2015-02-01

    Continuous subcutaneous insulin infusion (CSII) is increasing worldwide, mostly because of improved technology. The aim of this study was to evaluate the current status of CSII in Italy. Physicians from 272 diabetes centers received a questionnaire investigating clinical features, pump technology, and management of patients on CSII. Two hundred seventeen centers (79.8%) joined the study and, by the end of April 2013, gave information about 10,152 patients treated with CSII: 98.2% with type 1 diabetes mellitus, 81.4% adults, 57% female, and 61% with a conventional pump versus 39% with a sensor-augmented pump. CSII advanced functions were used by 68% of patients, and glucose sensors were used 12 days per month on average. Fifty-eight percent of diabetes centers had more than 20 patients on CSII, but there were differences among centers and among regions. The main indication for CSII was poor glucose control. Dropout was mainly due to pump wearability or nonoptimal glycemic control. Twenty-four hour assistance was guaranteed in 81% of centers. A full diabetes team (physician+nurse+dietician+psychologist) was available in 23% of adult-care diabetes centers and in 53% of pediatric diabetes units. CSII keeps increasing in Italy. More work is needed to ensure uniform treatment strategies throughout the country and to improve pump use.

  8. Continuous subcutaneous insulin infusion in diabetes: patient populations, safety, efficacy, and pharmacoeconomics.

    PubMed

    Pozzilli, Paolo; Battelino, Tadej; Danne, Thomas; Hovorka, Roman; Jarosz-Chobot, Przemyslawa; Renard, Eric

    2016-01-01

    The level of glycaemic control necessary to achieve optimal short-term and long-term outcomes in subjects with type 1 diabetes mellitus (T1DM) typically requires intensified insulin therapy using multiple daily injections or continuous subcutaneous insulin infusion. For continuous subcutaneous insulin infusion, the insulins of choice are the rapid-acting insulin analogues, insulin aspart, insulin lispro and insulin glulisine. The advantages of continuous subcutaneous insulin infusion over multiple daily injections in adult and paediatric populations with T1DM include superior glycaemic control, lower insulin requirements and better health-related quality of life/patient satisfaction. An association between continuous subcutaneous insulin infusion and reduced hypoglycaemic risk is more consistent in children/adolescents than in adults. The use of continuous subcutaneous insulin infusion is widely recommended in both adult and paediatric T1DM populations but is limited in pregnant patients and those with type 2 diabetes mellitus. All available rapid-acting insulin analogues are approved for use in adult, paediatric and pregnant populations. However, minimum patient age varies (insulin lispro: no minimum; insulin aspart: ≥2 years; insulin glulisine: ≥6 years) and experience in pregnancy ranges from extensive (insulin aspart, insulin lispro) to limited (insulin glulisine). Although more expensive than multiple daily injections, continuous subcutaneous insulin infusion is cost-effective in selected patient groups. This comprehensive review focuses on the European situation and summarises evidence for the efficacy and safety of continuous subcutaneous insulin infusion, particularly when used with rapid-acting insulin analogues, in adult, paediatric and pregnant populations. The review also discusses relevant European guidelines; reviews issues that surround use of this technology; summarises the effects of continuous subcutaneous insulin infusion on patients

  9. Continuous subcutaneous insulin infusion in diabetes: patient populations, safety, efficacy, and pharmacoeconomics

    PubMed Central

    Battelino, Tadej; Danne, Thomas; Hovorka, Roman; Jarosz‐Chobot, Przemyslawa; Renard, Eric

    2015-01-01

    Summary The level of glycaemic control necessary to achieve optimal short‐term and long‐term outcomes in subjects with type 1 diabetes mellitus (T1DM) typically requires intensified insulin therapy using multiple daily injections or continuous subcutaneous insulin infusion. For continuous subcutaneous insulin infusion, the insulins of choice are the rapid‐acting insulin analogues, insulin aspart, insulin lispro and insulin glulisine. The advantages of continuous subcutaneous insulin infusion over multiple daily injections in adult and paediatric populations with T1DM include superior glycaemic control, lower insulin requirements and better health‐related quality of life/patient satisfaction. An association between continuous subcutaneous insulin infusion and reduced hypoglycaemic risk is more consistent in children/adolescents than in adults. The use of continuous subcutaneous insulin infusion is widely recommended in both adult and paediatric T1DM populations but is limited in pregnant patients and those with type 2 diabetes mellitus. All available rapid‐acting insulin analogues are approved for use in adult, paediatric and pregnant populations. However, minimum patient age varies (insulin lispro: no minimum; insulin aspart: ≥2 years; insulin glulisine: ≥6 years) and experience in pregnancy ranges from extensive (insulin aspart, insulin lispro) to limited (insulin glulisine). Although more expensive than multiple daily injections, continuous subcutaneous insulin infusion is cost‐effective in selected patient groups. This comprehensive review focuses on the European situation and summarises evidence for the efficacy and safety of continuous subcutaneous insulin infusion, particularly when used with rapid‐acting insulin analogues, in adult, paediatric and pregnant populations. The review also discusses relevant European guidelines; reviews issues that surround use of this technology; summarises the effects of continuous subcutaneous insulin

  10. Reassessment of insulin dosing guidelines in continuous subcutaneous insulin infusion treated type 1 diabetes.

    PubMed

    King, Allen Bennett

    2014-06-01

    It is a daunting task to initiate or evaluate continuous subcutaneous insulin infusion, pump, dosing in a patient with type 1 diabetes. Choosing a low dose may lead to hyperglycemia or, too high, hypoglycemia. Mathematical dosing guidelines were used with the first human insulin injection in 1922. Since that time, they have been enlarged and modified. The current widely published guidelines were developed from retrospective evaluations of pump-downloads in patients without specified diet conditions or timed glucose testing. When diet is controlled and glucose testing is timed to evaluate post-meal excursions and during sleep, recent prospective studies found that these current dosing recommendations for basal insulin were too high and for bolus insulin too low. Further, simple mathematical interrelationships were published that kept the right proportions between the bolus dosing factors and the basal dose.

  11. Patient reactions to long-term outpatient treatment with continuous subcutaneous insulin infusion.

    PubMed Central

    Pickup, J C; Keen, H; Viberti, G C; Bilous, R W

    1981-01-01

    Fourteen of the first 15 insulin-dependent diabetics to be treated in our unit by three weeks or more of outpatient continuous subcutaneous insulin infusion with a portable syringe pump completed a questionnaire about their reactions to the system. Motivation was more important to a favourable response than occupation or intelligence. Most patients thought that diabetic control was better with the pump than conventional injection treatment and several felt subjectively better. Features such as the greater flexibility of diet and insulin delivery rates during continuous subcutaneous infusion were appreciated. The most consistent adverse criticism was about the size of the device used, nearly all patients thinking that smaller and lighter infusion systems should be developed. Psychological reactions to the infusion and difficulties with interpersonal relationships were identified; these must be clearly appreciated and discussed with patients and family before and during treatment. Nine of the 14 patients said they would undertake continuous subcutaneous infusion for one year and a further two said they would do so if the infuser was smaller. These results provide guidance on future technological development of continuous subcutaneous insulin infusion and indicate that the major constraint to long-term trials of the present system is the size of the pump. PMID:6783163

  12. Pascal's wager: combining continuous glucose monitoring and continuous subcutaneous insulin infusion.

    PubMed

    Kerr, David; Olateju, Tolu

    2010-06-01

    Pascal's Wager is a suggestion posed by the French Philosopher, Blaise Pascal, that even though the existence of God cannot be determined through reason, a person should wager that God exists because he or she has everything to gain and nothing to lose. In the area of consideration here, the optimum experimental trial of the combined use of continuous subcutaneous insulin infusion and real-time continuous glucose monitoring in free-living individuals with type 1 diabetes providing rock-solid evidence of clinical benefit has not been performed. Nevertheless, there is considerable enthusiasm for combining the technologies among healthcare professionals, patients, and manufacturers based on the belief that this approach to diabetes care must be beneficial beyond the available evidence (i.e., reason).

  13. An experimental study of pulsed micro-flows pertinent to continuous subcutaneous insulin infusion therapy

    NASA Astrophysics Data System (ADS)

    Wang, Bin; Demuren, Ayodeji; Gyuricsko, Eric; Hu, Hui

    2011-07-01

    An experimental study was conducted to investigate the unsteady micro-flow driven by an insulin pump commonly used in continuous subcutaneous insulin infusion (CSII) therapy. A microscopic particle image velocimetry (PIV) system was used to characterize the transient behavior of the micro-flow upon the pulsed excitation of the insulin pump in order to elucidate the underlying physics for a better understanding of the microphysical process associated with the insulin delivery in CSII therapy. The effects of air bubbles entrained inside the micro-sized CSII tubing system on the insulin delivery process were also assessed based on the micro-PIV measurements. While most solutions to insulin occlusion-related problems are currently based on clinical trials, the findings derived from the present study can be used to provide a better guidance for the troubleshooting of insulin occlusion in CSII therapy.

  14. Systematic review: continuous intraperitoneal insulin infusion with implantable insulin pumps for diabetes mellitus.

    PubMed

    Spaan, Nienke; Teplova, Alina; Stam, Gerrit; Spaan, Jos; Lucas, Cees

    2014-01-01

    Continuous intraperitoneal insulin infusion (CIPII) with implantable insulin pumps (IIPs) is a treatment option for diabetes, which is not widely utilized nor freely accessible in clinical practice. The aim of this study was to summarize available evidence on use of IIPs for CIPII for diabetes treatment, since its introduction to clinical use on the following outcomes: HbA1c, hypoglycaemic events, and complications of treatment. complications of diabetes and treatment satisfaction. Following the procedure for a systematic review this paper may contribute to a balanced evaluation of the need and effectiveness of IIPs. A pre-specified, registered protocol (CRD42012002150) was followed. Studies investigating all diabetes populations and types of IIPs were considered eligible. The sensitive search strategy was developed in collaboration with a clinical librarian and contents experts. PUBMED, MEDLINE, CENTRAL EMBASE, trial registries, and other databases were searched. References were screened independently by two authors, and decisions on study selection were recorded. Of the 1,703 references screened, 362 were assessed as potentially eligible. Ninety-four were identified as studies using IIPs. Fifteen papers, together reporting on four-randomized trials, and eight cohorts were included. Narrative analysis is provided, and data tables are available. CIPII by way of IIPs is effective in lowering HbA1c levels and reducing hypoglycaemic events. Superiority of IIP treatment is likely related to patient characteristics, one subgroup being patients unable to acquire satisfactory glycaemic control with subcutaneous insulin treatment. Higher treatment satisfaction was also reported for this subgroup. For these patients, risk of morbidity may be considered acceptable. Patients' perspectives, influence on quality of life, and possible other outcomes should also be considered important factors in weighing individual benefits and risks. A more uniform method of reporting would

  15. The Experiences of School Nurses Caring for Students Receiving Continuous Subcutaneous Insulin Infusion Therapy

    ERIC Educational Resources Information Center

    Darby, Wendy

    2006-01-01

    Diabetes mellitus is the most common metabolic disorder in childhood. Today, children with diabetes are receiving new technologically advanced treatment options, such as continuous subcutaneous insulin infusion (CSII) therapy. School nurses are the primary health caregivers of children with diabetes during school hours. Therefore, it is important…

  16. The Experiences of School Nurses Caring for Students Receiving Continuous Subcutaneous Insulin Infusion Therapy

    ERIC Educational Resources Information Center

    Darby, Wendy

    2006-01-01

    Diabetes mellitus is the most common metabolic disorder in childhood. Today, children with diabetes are receiving new technologically advanced treatment options, such as continuous subcutaneous insulin infusion (CSII) therapy. School nurses are the primary health caregivers of children with diabetes during school hours. Therefore, it is important…

  17. Insulin Lispro with Continuous Subcutaneous Insulin Infusion is Safe and Effective in Patients with Type 2 Diabetes: A Randomized Crossover Trial of Insulin Lispro Versus Insulin Aspart.

    PubMed

    Thrasher, James; Bhargava, Anuj; Rees, Tina M; Wang, Tao; Guzman, Cristina B; Glass, Leonard C

    2015-03-01

    This study provides clinical information regarding the use of insulin lispro versus insulin aspart in continuous subcutaneous insulin infusion (CSII) in adult patients with type 2 diabetes mellitus (T2D). After a 2-week lead-in period, 122 subjects treated with CSII therapy were randomized to 32 weeks of treatment during 2 separate 16-week treatment periods (TPs) with crossover beginning with insulin lispro (n = 60) or insulin aspart (n = 62). Glycated hemoglobin A1c (HbA1c), total daily insulin dose, and weight were recorded at the end of TP1 and TP2. Adverse events (AEs) and hypoglycemic events (overall, documented symptomatic, nocturnal, or severe) were recorded throughout the TPs. Data were analyzed using statistical methods that accounted for repeated measurements. A total of 107 subjects completed the study; 7 discontinued in TP1 and 8 discontinued in TP2. Insulin lispro was noninferior to insulin aspart in endpoint (weeks 16 and 32) HbA1c over TP1 and TP2 combined. Total daily insulin dose, weight change, and incidence and rates of hypoglycemia were not statistically significantly different between treatments. One case of severe hypoglycemia and 1 of diabetic ketoacidosis was observed with insulin aspart. One case of severe infusion site abscess was noted with insulin lispro. Overall, both insulin lispro and insulin aspart were well tolerated with similar AEs reported. Insulin lispro and insulin aspart performed similarly after 16 weeks of treatment, with noninferiority for HbA1c and no significant difference in parameters measured. These findings indicate that insulin lispro and insulin aspart can both be used safely and effectively in patients with T2D using CSII.

  18. Severe hypertriglyceridaemia in Type 2 diabetes mellitus: beneficial effect of continuous insulin infusion.

    PubMed

    Henderson, S R; Maitland, R; Mustafa, O G; Miell, J; Crook, M A; Kottegoda, S R

    2013-04-01

    Severe hypertriglyceridaemia is a recognized complication of Type 2 diabetes mellitus (T2DM); however, there is no consensus on acute management despite the significant risk of developing associated complications such as acute pancreatitis and hyperviscosity syndrome. To identify the association between hyperglycaemia and severe hypertriglyceridaemia in patients with T2DM and assess the effect of continuous insulin infusion therapy on serum triglyceride (TG) concentrations and report any adverse events associated with this therapeutic approach. Retrospective review of case records. Patients with uncontrolled hyperglycaemia and severe hypertriglyceridaemia (serum TG > 15 mmol/l) treated with continuous intravenous insulin infusion between October 2008 and September 2009 were retrospectively evaluated (n = 15). Details recorded included demographics, admission details, lipid profiles, glycaemic control, serum amylase and adverse events. Patients receiving treatment-dose unfractionated heparin infusion were excluded. Severe hypertriglyceridaemia is associated with hyperglycaemia in our heterogeneous group of patients with T2DM presenting with new-onset diabetes or established disease on pre-existing insulin or oral hypoglycaemic agents. Administration of continuous exogenous insulin not only achieved normoglycaemia but also dramatically corrected severe hypertriglyceridaemia in all patients (P = 0.001). The administration of continuous insulin in patients with T2DM with severe hypertriglyceridaemia is a simple and safe method of significantly reducing the immediate risk associated with this metabolic complication and should be considered in any T2DM patient presenting with severe hypertriglyceridaemia and hyperglycaemia.

  19. In vitro stability of insulin aspart in simulated continuous subcutaneous insulin infusion using a MiniMed 508 insulin pump.

    PubMed

    Senstius, J; Harboe, E; Westermann, H

    2007-02-01

    This study was designed to assess the stability and potency of insulin aspart under experimental circumstances simulating worst-case conditions during clinical use for continuous subcutaneous insulin infusion (CSII). The potency and stability of two batches of U100 insulin aspart, one recently manufactured and one nearing the end of shelf life, were evaluated after storage in a Medtronic (Northridge, CA) MiniMed 508 pump for up to 7 days at 37 +/- 2 degrees C. The pumps were placed on a vibrating platform (30 +/- 3 oscillations/min, 2 +/- 0.5 cm amplitude displacement) for 24 h/day to simulate movement by the pump user. The product remaining in the pump reservoir was tested at days 3, 4, and 7 and compared with control samples. After 7 days of in-pump use, there was no significant reduction in potency of insulin aspart or difference from reference values with regards to pH, isoAsp(B28), desamido insulin aspart, insulin aspart-related impurities, or high-molecular-weight proteins. The concentration of phenol and m-cresol remained at levels sufficient to ensure preservative efficacy for both control and test samples. There was no evidence of fibrillation or precipitation. The data indicate that storage in the plastic pump reservoir under temperature and vibration conditions simulating worst-case conditions during clinical use for CSII did not affect the stability or potency of insulin aspart significantly, and support an in-pump-use time of 7 days in the MiniMed 508 pump.

  20. Continuous subcutaneous insulin infusion with short-acting insulin analogues or human regular insulin: efficacy, safety, quality of life, and cost-effectiveness.

    PubMed

    Radermecker, Régis Pierre; Scheen, André Jacques

    2004-01-01

    Portable insulin infusion devices are effective and safe insulin delivery systems for managing diabetes mellitus, especially type 1 diabetes. Rapidly absorbed insulin analogues, such as insulin lispro or insulin aspart, may offer an advantage over regular human insulin for insulin pumps. Several open-label randomised crossover trials demonstrated that continuous subcutaneous insulin infusion (CSII) with insulin lispro provided a better control of postprandial hyperglycaemia and a slightly but significantly lower glycated haemoglobin level, with lower daily insulin requirement and similar or even less hypoglycaemic episodes. A CSII study comparing insulin lispro and insulin aspart demonstrated similar results with the two analogues, and better results than those with regular insulin. Because these analogues have a quicker onset and a shorter duration of action than regular insulin, one might expect an earlier and greater metabolic deterioration in case of CSII interruption, but a more rapid correction of metabolic abnormalities after insulin boluses when reactivating the pump. These expectations were confirmed in randomised protocols comparing the metabolic changes occurring during and after CSII interruption of various durations when the pump infused either insulin lispro or regular insulin. The extra cost resulting from the use of CSII and insulin analogues in diabetes management should be compensated for by better metabolic control and quality of life. In conclusion, CSII delivering fast-acting insulin analogues may be considered as one of the best methods to replace insulin in a physiological manner by mimicking meal and basal insulin requirements, without higher risk of hypoglycaemia or ketoacidosis in well-educated diabetic patients.

  1. Glycaemic control with continuous subcutaneous insulin infusion compared with intensive insulin injections in patients with type 1 diabetes: meta-analysis of randomised controlled trials

    PubMed Central

    Pickup, John; Mattock, Martin; Kerry, Sally

    2002-01-01

    Objective To compare glycaemic control and insulin dosage in people with type 1 diabetes treated by continuous subcutaneous insulin infusion (insulin infusion pump therapy) or optimised insulin injections. Design Meta-analysis of 12 randomised controlled trials. Participants 301 people with type 1 diabetes allocated to insulin infusion and 299 allocated to insulin injections for between 2.5 and 24 months. Main outcome measures Glycaemic control measured by mean blood glucose concentration and percentage of glycated haemoglobin. Total daily insulin dose. Results Mean blood glucose concentration was lower in people receiving continuous subcutaneous insulin infusion compared with those receiving insulin injections (standardised mean difference 0.56, 95% confidence interval 0.35 to 0.77), equivalent to a difference of 1.0 mmol/l. The percentage of glycated haemoglobin was also lower in people receiving insulin infusion (0.44, 0.20 to 0.69), equivalent to a difference of 0.51%. Blood glucose concentrations were less variable during insulin infusion. This improved control during insulin infusion was achieved with an average reduction of 14% in insulin dose (difference in total daily insulin dose 0.58, 0.34 to 0.83), equivalent to 7.58 units/day. Conclusions Glycaemic control is better during continuous subcutaneous insulin infusion compared with optimised injection therapy, and less insulin is needed to achieve this level of strict control. The difference in control between the two methods is small but should reduce the risk of microvascular complications. What is already known on this topicContinuous subcutaneous insulin infusion (insulin pump therapy) produces good long term control of blood glucose concentrations in people with type 1 diabetesControl of blood glucose concentration is substantially better on pump therapy than conventional (non-optimised) injection therapyIt is unclear how glycaemic control on pump therapy compares with modern optimised insulin

  2. Feasibility of adjacent insulin infusion and continuous glucose monitoring via the Medtronic Combo-Set.

    PubMed

    O'Neal, David N; Adhya, Sumona; Jenkins, Alicia; Ward, Glenn; Welsh, John B; Voskanyan, Gayane

    2013-03-01

    Subcutaneously infused insulin may interfere with the function of nearby glucose-sensing electrodes and vice versa. The prototype of the Combo-Set device (Medtronic) incorporates a subcutaneous insulin delivery catheter and continuous glucose monitoring (CGM) sensor assembled on the same platform and separated by 11 mm. We aim to evaluate Combo-Set's insulin delivery and glucose-sensing functions. Ten subjects with type 1 diabetes wore a Combo-Set and a Sof-Sensor inserted subcutaneously in contralateral abdominal areas connected to iPro recorders (Medtronic) for 53.25 ± 0.75 h (mean ± standard deviation). The Combo-Set delivered insulin diluent except during meal tests on days 1 and 3 when insulin lispro was delivered as a meal bolus and postmeal basal. Venous plasma samples were collected at the following time points from meal start: 0, 30, 60, 120, and 180 min for insulin measurements. The accuracy of the Combo-Set sensors was evaluated and compared with that of the Sof-Sensor, with each referenced against capillary glucose values (Contour Link Meter, Bayer). Accuracy of the Combo-Set sensor was comparable to that of the Sof-Sensor. Clarke error grid analysis showed that 97% of Combo-Set and 93% of Sof-Sensor values were in the A+B regions (p = .20, not significant). The Combo-Set showed the expected postbolus peak insulin time (67 ± 9 min, mean ± standard error). One "no delivery" alarm occurred during the 21 patient days of use. A device providing for simultaneous adjacent placement of an insulin infusion catheter and a CGM sensor is feasible and functions within acceptable limits. The low "no delivery" alarm rate was similar to that of other infusion sets. © 2013 Diabetes Technology Society.

  3. Specification and simulation of behavior of the Continuous Infusion Insulin Pump system.

    PubMed

    Babamir, Seyed Morteza; Dehkordi, Mehdi Borhani

    2014-01-01

    Continuous Infusion Insulin Pump (CIIP) system is responsible for monitoring diabetic blood sugar. In this paper, we aim to specify and simulate the CIIP software behavior. To this end, we first: (1) presented a model consisting of the CIIP system behavior in response to its environment (diabetic) behavior and (2) we formally defined the safety requirements of the system environment (diabetic) in the Z formal modeling language. Such requirements should be satisfied by the CIIP software. Finally, we programmed the model and requirements.

  4. Supporting patients with type 1 diabetes using continuous subcutaneous insulin infusion therapy: Difficulties, disconnections, and disarray.

    PubMed

    Perry, Lin; James, Steven; Gallagher, Robyn; Dunbabin, Janet; Steinbeck, Katharine; Lowe, Julia

    2017-08-01

    Use of continuous subcutaneous insulin infusion therapy in type 1 diabetes management is high. However, the incorporation of this technology into self-care is not without challenges, and the support of an appropriately skilled health care team is recommended. This study aimed to examine the support context for patients using continuous subcutaneous insulin infusion therapy from the health care professional perspective, as well as contextual influences for health care professionals and their patients. This ethnographic qualitative study was undertaken in New South Wales, Australia. Recruitment occurred using a snowball sampling technique, beginning with members of an established diabetes service group. Data were collected through the use of semistructured interviews undertaken by telephone and analysed using thematic analysis. Data were obtained from 26 interviews with staff from diverse professional backgrounds. An overarching theme of difficulties, disconnections, and disarray emerged, with findings indicating that participants perceived difficulties in relation to shortages of health care professional continuous subcutaneous insulin infusion-related expertise, and disconnected and disarrayed service structures and process, with barriers to access to these devices. Individual health care professionals were left to manage somehow or opted not to engage with related care. Findings provide insights from health care professionals' perspectives into the complexity of providing support for patients using continuous subcutaneous insulin infusion therapy across diverse contexts, and provide a platform for further research and service development. The need for consistent and coordinated care, and the infrastructure to facilitate this, flags an opportunity to drive integration of care and teamworking across as well as within settings and disciplines. © 2017 John Wiley & Sons, Ltd.

  5. Continuous subcutaneous insulin infusion versus multiple daily injections of insulin for pregnant women with diabetes.

    PubMed

    Farrar, Diane; Tuffnell, Derek J; West, Jane; West, Helen M

    2016-06-07

    Diabetes results in a rise in blood glucose above normal physiological levels; if untreated this may cause damage to many systems including the cardiovascular and renal systems. Pregnancy increases resistance to insulin action; for those women who have pre-gestational diabetes, this results in an increasing insulin requirement. There are several methods of administering insulin. Conventionally, insulin has been administered subcutaneously, formally referred to as intensive conventional treatment, but now more usually referred to as multiple daily injections (MDI). An alternative method of insulin administration is the continuous subcutaneous insulin infusion pump (CSII). To compare CSII with MDI of insulin for pregnant women with pre-existing and gestational diabetes. We searched the Cochrane Pregnancy and Childbirth Group's Trials Register (31 March 2016) and reference lists of retrieved studies. Randomised trials comparing CSII with MDI for pregnant women with diabetes. Three review authors independently assessed studies and two review authors extracted data. Disagreements were resolved through discussion with the third author. We assessed the quality of the evidence using the GRADE approach. We included five single-centre trials (undertaken in Italy) with 153 women and 154 pregnancies in this review.There were no clear differences in the primary outcomes reported between CSII and MDI in the included trials: caesarean section (risk ratio (RR) 1.09, 95% confidence interval (CI) 0.66 to 1.77; three trials, 71 women, evidence graded very low), large-for-gestational age (RR 4.15, 95% CI 0.49 to 34.95; three trials, 73 infants; evidence graded very low), and perinatal mortality (RR 2.33, 95% CI 0.38 to 14.32; four trials, 83 infants, evidence graded very low). Other primary outcomes were not reported in these trials (hypertensive disorders of pregnancy, development of type 2 diabetes, composite outcome of serious neonatal outcomes, and neurosensory disability

  6. [Treatment of diabetic coma and precoma with continuous low-dose insulin infusions (author's transl)].

    PubMed

    Luft, D; Schubert, W R; Reichenmiller, H E

    1976-11-26

    13 patients, nine women and four men, aged 22 to 83 years, were treated for diabetic coma or precoma between September 1974 and January 1976. Ten patients were known diabetics and six of them had been treated with insulin. On admission blood sugar was 32.4 +/- 3.3 mmol/l (5.84 +/- 0.6 g/l). The capillary blood pH was 7.15 +/- 0.06 (n = 13). Treatment consisted of continuous insulin infusion (6 IU soluble insulin/hour), physiological saline, potassium substitution and sodium bicarbonate (if the pH was below 7.15). In the first hours of treatment 98 +/- 12IU of insulin, 6.5 +/- 0.5 litres of fluid, 168 +/- 22 mmol of potassium and 237 +/- 55 mmol NaHCO3 were required. During the first 4 hours of the insulin infusion the blood sugar decrease per hour was 3.55 mmol/l (0.64 g/l). Hypokalaemia during treatment occurred in one case, hypoglycaemia was not observed. A preceding treatment with insulin and severe acidosis did not influence therapeutic success. Twelve patients were treated successfully, one patient died 6 hours after admission following mesenteric arterial embolism.

  7. Guidelines for Application of Continuous Subcutaneous Insulin Infusion (Insulin Pump) Therapy in the Perioperative Period

    PubMed Central

    Boyle, Mary E; Seifert, Karen M; Beer, Karen A; Apsey, Heidi A; Nassar, Adrienne A; Littman, Stephanie D; Magallanez, Janice M; Schlinkert, Richard T; Stearns, Joshua D; Hovan, Michael J; Cook, Curtiss B

    2012-01-01

    Case reports indicate that diabetes patients receiving outpatient insulin pump therapy have been allowed to continue treatment during surgical procedures. Although allowed during surgery, there is actually little information in the medical literature on how to manage patients receiving insulin pump therapy during a planned surgical procedure. A multidisciplinary work group reviewed current information regarding the use of insulin pumps in the perioperative period. Although the work group identified safety issues specific to surgical scenarios, it believed that with the use of standardized guidelines and a checklist, continuation of insulin pump therapy during the perioperative period is feasible. A sample set of protocols have been developed and are summarized. A policy outlining clear procedures should be established at the institutional level to guide physicians and other staff if the devices are to be employed during the perioperative period. Additional clinical experience with the technology in surgical scenarios is needed, and consensus should be developed for insulin pump use in the perioperative phases of care. PMID:22401338

  8. [Consensus document on continuous subcutaneous insulin infusion (CSII) treatment in paediatrics with type I diabetes].

    PubMed

    Barrio Castellanos, R; García Cuartero, B; Gómez Gila, A; González Casado, I; Hermoso López, F; Luzuriaga Tomás, C; Oyarzabal Irigoyen, M; Rica Etxebarria, I; Rodríguez Rigual, M; Torres Lacruz, M

    2010-05-01

    This article reports on the Spanish Position Statement for the Diabetes Pediátric Group for the Spanish Pediatric Endocrinology Society (SEEP) on continuous subcutaneous insulin infusion in children and adolescents with type 1 diabetes. The practical issues about their indications, appropriate candidates, feasibility, and limits are outlined. The conclusions are based on the comprehensive review and balanced assessment of the evidence base on the international consensus and consensual answers to these questions for the participants. Copyright 2009 Asociación Española de Pediatría. Published by Elsevier Espana. All rights reserved.

  9. Overnight versus 24 hours of continuous subcutaneous insulin infusion as supplement to oral antidiabetic drugs in type 2 diabetes.

    PubMed

    Parkner, Tina; Laursen, Torben; Chen, Jian-Wen; Møller, Marianne K; Thomsen, Henrik F; Jørgensen, Christina; Smedegaard, Jørgen S; Lauritzen, Torsten; Christiansen, Jens S

    2007-09-01

    Basal continuous subcutaneous insulin infusion (CSII) therapy at a fixed rate may effectively improve glycemic control in patients with type 2 diabetes when oral antidiabetic treatment fails. Regimens of simple constant subcutaneous delivery of insulin may provide theoretical advantages in type 2 diabetes. Ten subjects with type 2 diabetes who obtained insufficient glycemic control on oral antidiabetic drugs were included. Following an initial control day, two periods of 3 days with CSII of a rapid-acting insulin analogue, 1.5 IU/h (dose obtained from a preceding study), for 8 hours overnight and for 24 hours, respectively, were carried out in random order. Profiles of serum insulin aspart, serum endogenous insulin, and plasma glucose were recorded. Compared to the control day, an 8-hour overnight insulin infusion during a 3-day period improved fasting plasma glucose (FPG) (mean differences +/- SEM; Delta59.0 +/- 10.1 mg/dl; p < 0.01) and 2-hour postprandial plasma glucose (PPPG) (Delta57.8 +/- 10.6 mg/dl; p < 0.01) after breakfast. Compared to an 8-hour overnight infusion, a 24-hour infusion further improved all three PPPG values after breakfast, lunch, and dinner (Delta28.8 +/- 8.1 mg/dl, Delta30.6 +/- 8.1 mg/dl, and Delta35.1 +/- 7.9 mg/dl; p < 0.01). During insulin infusion, only one hypoglycemic episode with PG <55.8 mg/dl and mild symptoms was recorded. Continuous subcutaneous insulin infusion with a rapid-acting insulin analogue at a fixed rate of 1.5 IU/h, either overnight or for 24 hours, improved glycemic control without safety concerns in patients with type 2 diabetes who had secondary failure to oral antidiabetic drugs. The effect on FPG was similar for both treatments, whereas the effect on PPPG was superior when insulin was infused during the entire 24 hours.

  10. Position Statement on the management of continuous subcutaneous insulin infusion (CSII): The Italian Lazio experience.

    PubMed

    Maurizi, Anna R; Suraci, Concetta; Pitocco, Dario; Schiaffini, Riccardo; Tubili, Claudio; Morviducci, Lelio; Giordano, Renato; Manfrini, Silvia; Lauro, Davide; Frontoni, Simona; Pozzilli, Paolo; Buzzetti, Raffaella

    2016-01-01

    This document has been developed by a group of Italian diabetologists with extensive experience in continuous subcutaneous insulin infusion (CSII) therapy to provide indications for the clinical management of CSII in diabetic patients (both type 1 and type 2) based on delivery mode operating in Italy. Although the potential benefits of pump therapy in achieving glycemic goals is now accepted, such results cannot be obtained without specific knowledge and skills being conveyed to patients during ad hoc educational training. To ensure that these new technologies reach their full effectiveness, as demonstrated theoretically and clinically, a careful assessment of the overall therapeutic and educational process is required, in both qualitative and quantitative terms. Therefore, to ensure the cost-effectiveness of insulin pump therapy and to justify reimbursement of therapy costs by the National Health System in Italy, in this article we present a model for diabetes and healthcare centers to follow that provides for different levels of expertise in the field of CSII therapy. This model will guarantee the provision of excellent care during insulin pump therapies, thus representing the basis for a successful outcome and expansion of this form of insulin treatment in patients with diabetes while also keeping costs under control. © 2015 Ruijin Hospital, Shanghai Jiaotong University School of Medicine and Wiley Publishing Asia Pty Ltd.

  11. Lower dose basal insulin infusion has positive effect on glycaemic control for children with type I diabetes on continuous subcutaneous insulin infusion therapy.

    PubMed

    Schulten, Ron J; Piet, Jessica; Bruijning, Patricia Cjl; de Waal, Wouter J

    2017-02-01

    The aim of our study was to explore a possible relationship between proportion of basal insulin dose (%BD/T) and glycaemic control in children with type I diabetes on continuous subcutaneous insulin infusion (CSII) therapy. All patients under the age of 18 with type I diabetes mellitus, treated in a general hospital in Utrecht, The Netherlands, who were on CSII therapy between 2000 and 2011 were selected for inclusion. All data as recorded during outpatient visits were retrospectively collected from patients' charts. Analyses were performed using R Statistical Software. Data of 847 outpatient visits of 78 patients [31 males (39.7%) and 47 females (60.3%)] were analyzed. Mean age at diagnosis was 7.1 ± 3.7 yr, mean age at start of pump therapy 10.1 ± 3.8 yr. Mean HbA1c before pump start was 8.3 ± 1.0%, median BMI standard deviation score for age and gender was 0.64 (-1.89-3.79). Median follow-up time per patient was 29 months with an average of 10 visits (range: 3-25). Multivariate analysis revealed that a change of 10% in %BD/T resulted in a decrease or increase of HbA1c of 0.22% [95% confidence interval (CI): 0.15-0.29). No significant effect was observed from SDS BMI, sex, or duration of diabetes. Low dose basal insulin infusion as a percentage of total insulin dose has a positive effect on metabolic outcome as expressed in HbA1c-levels. A change of 10% in %BD/T results in a decrease or increase of HbA1c of 0.22%. This supports the tendency to aim at the lowest basal insulin requirements in pump setting strategy. © 2016 John Wiley & Sons A/S. Published by John Wiley & Sons Ltd.

  12. Comparison of continuous subcutaneous insulin infusion and multiple daily insulin injections in Chinese patients with type 2 diabetes mellitus.

    PubMed

    Yang, Honghong; Heng, Xueyuan; Liang, Cuige; Liu, Xiaomeng; Du, Wenhua; Li, Shoujie; Wang, Yueli; Dong, Qingyu; Li, Wenxia; Pan, Zhenyu; Gong, Qian; Gao, Guanqi

    2014-08-01

    To investigate prospectively the insulin dose requirements of Chinese patients with type 2 diabetes mellitus treated with either multiple daily insulin injections (MDI) or continuous subcutaneous insulin infusion (CSII) therapy during a 2-week therapeutic intervention. Patients with type 2 diabetes mellitus were randomly assigned to MDI or CSII therapy. The effects of the two treatment methods were determined based on blood glucose parameters, total daily insulin dose and rates of hypoglycaemia. A total of 609 patients were enrolled in the study. Glycaemic goals were achieved after a mean ± SD of 6.90 ± 2.10 and 5.44 ± 2.22 days' treatment in the MDI and CSII groups, respectively. Once stabilized, the mean ± SD total daily insulin doses were 37.12 ± 10.19 IU and 32.58 ± 8.78 IU for the MDI and CSII groups, respectively. Once stabilized, the mean ± SD total basal and bolus doses were 19.46 ± 7.95 IU/day and 17.66 ± 3.53 IU/day for the MDI group, and 22.79 ± 7.55 IU/day and 9.81 ± 2.64 IU/day for the CSII group, respectively. There were significant differences in the total, basal and bolus insulin doses between the two groups. CSII therapy may be considered as an effective method to achieve good glycaemic control in Chinese patients with type 2 diabetes mellitus. © The Author(s) 2014 Reprints and permissions: sagepub.co.uk/journalsPermissions.nav.

  13. Continuous subcutaneous insulin infusion (CSII) in the Veneto region: efficacy, acceptability and quality of life.

    PubMed

    Bruttomesso, D; Pianta, A; Crazzolara, D; Scaldaferri, E; Lora, L; Guarneri, G; Mongillo, A; Gennaro, R; Miola, M; Moretti, M; Confortin, L; Beltramello, G P; Pais, M; Baritussio, A; Casiglia, E; Tiengo, A

    2002-08-01

    To study the effect of continuous subcutaneous insulin infusion (CSII) on metabolic control and well-being in patients with Type 1 diabetes. Efficacy, safety and interference with everyday life associated with CSII were studied retrospectively in 138 diabetic patients from the Veneto region treated for 7.4 +/- 0.4 years. Glycosylated haemoglobin decreased during the first year of CSII from 9.3 +/- 0.2% to 7.9 +/- 0.1% (P < 0.0001), and then remained unchanged. Serious hypoglycaemia decreased from 0.31 +/- 0.07/year to 0.09 +/- 0.02/year (P < 0.003), as did ketoacidosis (from 0.41 +/- 0.12/year to 0.11 +/- 0.03/year, P < 0.013). During the first year of therapy daily insulin requirement decreased from 49 +/- 1 to 42 +/- 2 U/day (P < 0.0001) and did not change thereafter. The number of out-patient consultations and hospital admissions per year also decreased significantly. CSII was associated with a progressive increase of body weight (P < 0.05) and with 0.2 +/- 0.04 infections/patient per year at the infusion site. Infection was rated as mild in 72%, moderate in 18%, severe in 10%. Patients reported that CSII improved metabolic control (71%), sense of well-being (41%), and allowed more freedom (40%). Quality of life, assessed using the DQOL, after 7 years of CSII was rated as good by patients (score of 73.0 +/- 1.8 on a scale from 0 to 100). This retrospective analysis suggests that CSII improves metabolic control in Type 1 diabetic patients, reduces hypoglycaemic and ketoacidotic events, is well accepted, allows a good quality of life and decreases out-patient consultations and hospital admissions.

  14. Multicenter User Evaluation of ACCU-CHEK® Combo, an Integrated System for Continuous Subcutaneous Insulin Infusion

    PubMed Central

    Kerr, David; Hoogma, Roel P.L.M; Buhr, Andreas; Petersen, Bettina; Storms, Fred E.M.G

    2010-01-01

    Background The aim of this study was to evaluate a newly developed system for insulin delivery incorporating a multifunctional blood glucose meter and a remotely controlled insulin pump (ACCU-CHEK® Combo system) in established pump users with type 1 diabetes. The technology was assessed both from device performance and subject usability perspectives. Method A multicenter, prospective, single group study was carried out in five centers in the Netherlands and four centers in the United Kingdom for more than 6 months. The study was divided into two phases: Phase 1 (4 weeks) for device validation purposes and phase 2 (22 weeks) to observe the impact of the system on metabolic control, patient satisfaction [using the Diabetes Treatment Satisfaction Questionnaire (DTSQ)] and device safety. Results Eighty subjects completed the planned study period. There were no unexpected device errors. Treatment satisfaction was high at baseline and further increased to study end (DTSQ change version: sum score, 10.6 ± 7.2; scale score range, -18 to +18, p < 0.0001). Hemoglobin A1c improved continuously over time, from 7.9% (±0.9%) to 7.7% (±0.8%) at month 3 (p < 0.001) and 7.6% (±0.8%) at month 6 (p < 0.0001). The frequency of severe hypoglycemia was 0.08 per patient years. There was no case of ketoacidosis. Conclusions The new system was evaluated by experienced continuous subcutaneous insulin infusion users as safe in daily practice and associated with favorable treatment satisfaction and a modest improvement in glycemic control. PMID:21129336

  15. Retrospective evaluation of continuous rate infusion of regular insulin intravenously for the management of feline diabetic ketoacidosis.

    PubMed

    Bollinger, Pamela N; Moore, Lisa E

    2015-01-01

    The use and efficacy of continuous rate infusion (CRI) of regular insulin intravenously for the treatment of feline diabetic ketoacidosis was retrospectively evaluated. The study focused on the rate of glucose decline, time to resolution of inappetence, time to long-term injectable insulin, and length of hospital stay. Review of medical records from 2009 to 2011 identified 10 cases that met the inclusion criteria. Six cats were existing diabetics, 3 of whom had recent insulin changes. Five cats had concurrent diseases. The mean time to long-term injectable insulin was 55 hours. The mean length of hospitalization was 3.8 days. Five cats survived to discharge. In 5 patients, an insulin CRI permitted a short hospital stay and transition to long-term injectable insulin. Many cats with diabetic ketosis or diabetic ketoacidosis are prior diabetics with concurrent disease and/or a history of recent insulin changes.

  16. Overnight versus 24 Hours of Continuous Subcutaneous Insulin Infusion as Supplement to Oral Antidiabetic Drugs in Type 2 Diabetes

    PubMed Central

    Parkner, Tina; Laursen, Torben; Chen, Jian-Wen; Møller, Marianne K.; Thomsen, Henrik F.; Jørgensen, Christina; Smedegaard, Jørgen S.; Lauritzen, Torsten; Christiansen, Jens S.

    2007-01-01

    Background Basal continuous subcutaneous insulin infusion (CSII) therapy at a fixed rate may effectively improve glycemic control in patients with type 2 diabetes when oral antidiabetic treatment fails. Regimens of simple constant subcutaneous delivery of insulin may provide theoretical advantages in type 2 diabetes. Methods Ten subjects with type 2 diabetes who obtained insufficient glycemic control on oral antidiabetic drugs were included. Following an initial control day, two periods of 3 days with CSII of a rapid-acting insulin analogue, 1.5 IU/h (dose obtained from a preceding study), for 8 hours overnight and for 24 hours, respectively, were carried out in random order. Profiles of serum insulin aspart, serum endogenous insulin, and plasma glucose were recorded. Results Compared to the control day, an 8-hour overnight insulin infusion during a 3-day period improved fasting plasma glucose (FPG) (mean differences ± SEM; Δ59.0 ± 10.1 mg/dl; p < 0.01) and 2-hour postprandial plasma glucose (PPPG) (Δ57.8 ± 10.6 mg/dl; p < 0.01) after breakfast. Compared to an 8-hour overnight infusion, a 24-hour infusion further improved all three PPPG values after breakfast, lunch, and dinner (Δ28.8 ± 8.1 mg/dl, Δ30.6 ± 8.1 mg/dl, and Δ35.1 ± 7.9 mg/dl; p < 0.01). During insulin infusion, only one hypoglycemic episode with PG <55.8 mg/dl and mild symptoms was recorded. Conclusion Continuous subcutaneous insulin infusion with a rapid-acting insulin analogue at a fixed rate of 1.5 IU/h, either overnight or for 24 hours, improved glycemic control without safety concerns in patients with type 2 diabetes who had secondary failure to oral antidiabetic drugs. The effect on FPG was similar for both treatments, whereas the effect on PPPG was superior when insulin was infused during the entire 24 hours. PMID:19885138

  17. Comparison of Insulin Pump Therapy (Continuous Subcutaneous Insulin Infusion) to Alternative Methods for Perioperative Glycemic Management in Patients with Planned Postoperative Admissions

    PubMed Central

    Corney, Sarah M.; Dukatz, Tamra; Rosenblatt, Solomon; Harrison, Barbara; Murray, Robert; Sakharova, Alla; Balasubramaniam, Mamtha

    2012-01-01

    Background Patients with diabetes who use insulin pumps [continuous subcutaneous insulin infusion (CSII)] undergo surgeries that require postoperative hospital admission. There are no defined guidelines for CSII perioperative use. Methods This retrospective single-institution study identified type 1 and type 2 diabetes subjects by electronically searching 2005–2010 anesthesia preoperative assessments for “pump.” Surgical cases (n = 92) were grouped according to intraoperative insulin delivery method: (a) CSII continuation of basal rate with/without correctional insulin bolus(es) (n = 53); (b) conversion to intravenous insulin infusion (n = 20); and (c) CSII suspension with/without correctional insulin bolus(es) (n = 19). These groups were compared on mean intraoperative blood glucose (BG) and category of most extreme intraoperative BG. Results Differences were found on baseline characteristics of diabetes duration (p = .010), anesthesia time (p = .011), proportions receiving general anesthesia (p = .013), and preoperative BG (p = .033). The conversion group had the longest diabetes duration and anesthesia time; it had a higher proportion of general anesthesia recipients and a higher mean preoperative BG than the continuation group. There was no significant difference in mean BG/surgical case between continuation (163.5 ± 58.5 mg/dl), conversion (152.3 ± 28.9 mg/dl), and suspension groups (188.3 ± 44.9 mg/dl; p = .128). The suspension group experienced a greater percentage of cases (84.2%) with one or more intraoperative BG > 179 mg/dl than continuation (45.3%) and conversion (40%) groups Figure 1 groupings (p = .034). Conclusions In this limited sample, preliminary findings are consistent with similar intraoperative glycemic control between CSII continuation and CSII conversion to intravenous insulin infusions. Continuous subcutaneous insulin infusion suspension had a greater rate of hyperglycemia. Preoperative differences between insulin delivery groups

  18. Successful treatment of young infants presenting neonatal diabetes mellitus with continuous subcutaneous insulin infusion before genetic diagnosis.

    PubMed

    Rabbone, Ivana; Barbetti, Fabrizio; Marigliano, Marco; Bonfanti, Riccardo; Piccinno, Elvira; Ortolani, Federica; Ignaccolo, Giovanna; Maffeis, Claudio; Confetto, Santino; Cerutti, Franco; Zanfardino, Angela; Iafusco, Dario

    2016-08-01

    Neonatal diabetes mellitus (NDM) is defined as hyperglycemia and impaired insulin secretion with onset within 6 months of birth. While rare, NDM presents complex challenges regarding the management of glycemic control. The availability of continuous subcutaneous insulin infusion pumps (CSII) in combination with continuous glucose monitoring systems (CGM) provides an opportunity to monitor glucose levels more closely and deliver insulin more safely. We report four cases of young infants with NDM successfully treated with CSII and CGM. Moreover, in two cases with Kir 6.2 mutation, we describe the use of CSII in switching therapy from insulin to sulfonylurea treatment. Insulin pump requirement for the 4 neonatal diabetes cases was the same regardless of disease pathogenesis and c-peptide levels. No dilution of insulin was needed. The use of an integrated CGM system helped in a more precise control of BG levels with the possibility of several modifications of insulin basal rates. Moreover, as showed in the first two case-reports, when the treatment was switched from insulin to glibenclamide, according to identification of Kir 6.2 mutation and diagnosis of NPDM, the CSII therapy demonstrated to be helpful in allowing gradual insulin suspension and progressive introduction of sulfonylurea. During the neonatal period, the use of CSII therapy is safe, more physiological, accurate and easier for the insulin administration management. Furthermore, CSII therapy is safe during the switch of therapy from insulin to glibenclamide for infants with permanent neonatal diabetes mellitus.

  19. Opinions and Satisfaction Regarding Continuous Subcutaneous Insulin Infusion Therapy in Adult Patients with Type 1 Diabetes

    PubMed Central

    Nishio, Ikuko; Chujo, Masami; Ohkura, Tsuyoshi; Kataoka, Hideyuki

    2015-01-01

    Background This study examined the treatment satisfaction of type 1 diabetic patients undergoing continuous subcutaneous insulin infusion (CSII) therapy, and patients’ thoughts regarding CSII. Methods We provided a self-administered questionnaire survey over the internet. Participants were 106 individuals with type-one diabetes aged 20 years or older, undergoing CSII. The survey examined patients’ treatment satisfaction, and their thoughts regarding CSII. Descriptive statistics were calculated. We compared relationships between treatment satisfaction and other variables using the Kruskal-Wallis rank sum test, and performed content analysis on participants’ thoughts regarding CSII. Results Regarding treatment satisfaction, the response, “neither of them” was the most frequent. Comparing relationships between treatment satisfaction and other variables, significant differences were found for the variables “age,” “presence of dissatisfaction regarding doctors’ response,” and “presence of a significant medical expense burden.” Participants’ thoughts regarding CSII were classified into 10 categories. Conclusion Participants expressed positive evaluations, such as that their blood sugar control had improved due to CSII, and that they perceived improvement in their health. Participants also expressed negative evaluations, however, such as that medical expenses resulting from CSII were high, and that these expenses may cause distress and future economic insecurity. In future, patients may benefit from nursing support that allows patients to confidently continue with CSII. PMID:26538796

  20. A Comparison of Continuous Subcutaneous Insulin Infusion vs. Multiple Daily Insulin Injection in Children with Type I Diabetes in Kuwait: Glycemic Control, Insulin Requirement, and BMI

    PubMed Central

    Mousa, Mohammad; Al-Mahdi, Maria; Al-Sanaa, Hala; Al-Kandari, Hessa

    2015-01-01

    Objective Continuous subcutaneous insulin infusion (CSII) and multiple daily insulin injections (MDI) are two methods currently used to manage type I diabetes mellitus (T1DM). Here we compare our experiences with CSII and MDI in a large cohort of pediatric patients in Kuwait. Methods Data on 326 patients with T1DM who were started on CSII between 2007 and 2012 were retrospectively compared with those of 326 patients on MDI. They were matched for sex, age at diagnosis, T1DM duration, glycemic control, insulin requirement, and body mass index (BMI). Data were collected at baseline and every three months and included glycated hemoglobin (HbA1c), insulin dose, and adverse events (severe hypoglycemia, diabetic ketoacidosis, and skin problems). Results The main reason for switching to CSII was to achieve better glycemic control (37%), followed by reducing hypoglycemia, and improving the quality of life (13.3% each). Although HbA1c decrease was most significant in the first year, it continued to be significantly lower in the CSII group compared to the MDI throughout the study period. Total daily insulin requirements were significantly lower in the CSII group. BMI increased in both groups, but the difference was significant only at the end of the fifth year. There was no significant change in the rate of diabetic ketoacidosis in either group. The CSII patients had more severe hypoglycemic episodes at baseline; however, it significantly decreased throughout the study period. Only five patients discontinued CSII therapy and two of these restarted within three months. Conclusion CSII is a safe intensive insulin therapy in youngsters with T1DM and achieved markedly fewer severe hypoglycemic episodes and lower daily insulin requirements PMID:26421114

  1. [Current status of continuous subcutaneous insulin infusion and continuous glucose monitoring systems in the Community of Madrid].

    PubMed

    Arranz Martín, Alfonso; Calle Pascual, Alfonso; Del Cañizo Gómez, Francisco Javier; González Albarrán, Olga; Lisbona Gil, Arturo; Botella Serrano, Marta; Pallardo Sánchez, Luis Felipe

    2015-04-01

    To analyze the available information about continuous subcutaneous insulin infusion (CSII) and continuous glucose monitoring (CGM) systems in the public health care system of the Community of Madrid. A survey consisting of 31 items was sent to the 28 endocrinology department of the Madrid public hospitals. Items focused on CSII and CGM and included patients' registrations, as well as data regarding healthcare, administrative, and logistic aspects. Responses from a total of 20 hospitals where these procedures are used were received from March 2013 to May 2014. Data about pediatric patients were obtained from adult endocrinology departments, except for two hospitals which directly reported the information. A total of 1256 CSII pumps were recorded in the Madrid region, of which 1089 were used by adults, and the remaining 167 by pediatric patients. During 2013, 151 new CSII systems were implanted (12% of the total), while 14 pumps were withdrawn. Availability of human resources (medical assistance) and the number of staff practitioners experienced in management of these systems widely varied between hospitals. Eighty-five percent of hospitals used retrospective CGM systems, and 40% routinely placed them before starting an insulin pump. Thirteen hospitals (65%) used long-term, real-time CGM systems in selected cases (a total of 67 patients). Use of these technologies in diabetes is unequal between public health care hospitals in Madrid, and is still significantly lower as compared to other countries with similar incomes. However, there appears to be a trend to an increase in their use. Copyright © 2014 SEEN. Published by Elsevier España, S.L.U. All rights reserved.

  2. Continuous subcutaneous insulin infusion versus multiple daily injections in individuals with type 1 diabetes: a systematic review and meta-analysis.

    PubMed

    Benkhadra, Khalid; Alahdab, Fares; Tamhane, Shrikant U; McCoy, Rozalina G; Prokop, Larry J; Murad, Mohammad Hassan

    2017-01-01

    The relative efficacy of continuous subcutaneous insulin infusion and multiple daily injections in individuals with type 1 diabetes is unclear. We sought to synthesize the existing evidence about the effect of continuous subcutaneous insulin infusion on glycosylated hemoglobin, hypoglycemic events, and time spent in hypoglycemia compared to multiple daily injections. We searched MEDLINE, EMBASE, Cochrane Central Register of Controlled Trials and Database of Systematic Reviews, and Scopus from January 2008 through November 2015 for randomized controlled trials that enrolled children or adults with type 1 diabetes. Trials identified in a previous systematic review and published prior to 2008 were also included. We included 25 randomized controlled trials at moderate risk of bias. Meta-analysis showed a significant reduction in glycosylated hemoglobin in patients treated with continuous subcutaneous insulin infusion compared to multiple daily injections (mean difference 0.37; 95 % confidence interval, 0.24-0.51). This effect was demonstrated in both children and adults. There was no significant difference in minor or severe hypoglycemic events. Continuous subcutaneous insulin infusion was associated with lower incidence of nocturnal hypoglycemia. There was no significant difference in the time spent in hypoglycemia. In children and adults with type 1 diabetes and compared to multiple daily injections, continuous subcutaneous insulin infusion is associated with a modest reduction in glycosylated hemoglobin. There was no difference in severe or minor hypoglycemia, but likely a lower incidence of nocturnal hypoglycemia with continuous subcutaneous insulin infusion.

  3. Continuous Subcutaneous Insulin Infusion as an Effective Method of Desensitization Therapy for Diabetic Patients with Insulin Allergy: A 4-year Single-center Experience.

    PubMed

    Yuan, Tao; Zhao, Weigang; Wang, Lianglu; Dong, Yingyue; Li, Naishi

    2016-11-01

    This article summarizes our experiences in the application of continuous subcutaneous insulin infusion (CSII) as a method of rapid desensitization therapy for diabetic patients with insulin allergy that was subsequently switched to a regimen of multiple-dose injections for long-term insulin therapy. The clinical data of 11 diabetic patients with insulin allergy in Peking Union Medical College Hospital from April 1, 2008, through December 31, 2011, were retrospectively analyzed. All 11 conditions were diagnosed by case history, skin testing, determination of serum specific anti-insulin IgE, and reaction to withdrawal of insulin. Seven patients accepted the traditional injection method of desensitization, and 5 patients accepted CSII with the protocol designed for this study (1 patient accepted CSII after failure by the formal method). Six of the 7 patients who accepted the traditional method and all 5 patients who accepted CSII had successful results. All 5 patients in the CSII group switched to a regimen of multiple dosage injections. In a survey of 28 nurses, both experienced nurses and practical nurses preferred to use CSII as the method of desensitization. It is feasible and effective for diabetic patients with insulin allergy to use CSII as a method of rapid desensitization with subsequent switching to a regimen of multiple-dose injections for long-term insulin therapy. Copyright © 2016 Elsevier HS Journals, Inc. All rights reserved.

  4. Computerised insulin dosing calculators for the management of continuous insulin infusions after cardiac surgery: A systematic review and meta-analysis.

    PubMed

    Higgs, Megan H; Fernandez, Ritin S

    2017-04-01

    To investigate the effectiveness of computerised insulin dosing calculators for the management of continuous insulin infusions in adult patients who underwent cardiac surgery. A systematic review was conducted. The CINAHL, MEDLINE and Cochrane databases were searched for primary studies that compared a computerised insulin dosing calculator to a paper protocol. The main outcome measures were mean Blood Glucose Level (BGL), time to achieve BGL target range, time spent within BGL target range, the incidence of hyperglycaemia and the incidence of hypoglycaemia. Five studies were included in the final review. Pooled data demonstrated significant improvements in mean BGL (MD -14.24, 95% CI -26.93 to -1.55), p=0.03 and significantly lower rates of hypoglycaemia (OR 0.038, 95% CI: 0.16-0.90), p=0.03 amongst the computer calculator groups in comparison to the paper protocol groups. No significant difference in the incidence of severe hypoglycaemia was demonstrated (OR 0.21, 95% CI 0.02-1.79), p=0.15. No difference was found in time (hours) to reach target blood glucose range (MD -1.47, 95% CI -3.75 to 0.81), p=0.21. There is some evidence to support the use of computerised insulin dosing calculators for insulin infusion management within critical care environments. Copyright © 2016 Elsevier Ltd. All rights reserved.

  5. Changes in Basal Insulin Infusion Rates With Subcutaneous Insulin Infusion

    PubMed Central

    Heinemann, Lutz; Nosek, Leszek; Kapitza, Christoph; Schweitzer, Matthias-Axel; Krinelke, Lars

    2009-01-01

    OBJECTIVE Evaluation of the time required until a change in the basal insulin infusion rate with an insulin pump induces subsequent changes in the metabolic effect. RESEARCH DESIGN AND METHODS In this euglycemic glucose clamp study, 10 male subjects with type 1 diabetes received three different subcutaneous insulin infusion rates (0.5, 1.0, and 2.0 units/h; for 4 h each) of insulin lispro (IL) with insulin pumps. RESULTS An increase in insulinemia occurred within 15–30 min after changing the infusion rate. While the serum IL levels reached a steady state at the end of the infusion period, the glucose infusion rates did not always reach steady-state levels with the higher infusion rates. However, an increase in the glucose consumption occurred within 30–60 min after switching the infusion rate. CONCLUSIONS Several hours are required until a new steady state in the metabolic effect is achieved after a significant change in basal insulin infusion. PMID:19487635

  6. Fields of application of continuous subcutaneous insulin infusion in the treatment of diabetes and implications in the use of rapid-acting insulin analogues.

    PubMed

    Pitocco, D; Rizzi, A; Scavone, G; Tanese, L; Zaccardi, F; Manto, A; Ghirlanda, G

    2013-09-01

    In western countries, diabetes mellitus, because of macrovascular and microvascular complications related to it, is still an important cause of death. Patients with type 1 diabetes mellitus (T1DM) have a six-time higher risk of mortality than healthy patients. Since the Diabetes Control and Complications Trial (DCCT) established how an intensive therapy is necessary to prevent diabetes mellitus complications, many studies have been conducted to understand which method is able to reach an optimal metabolic control. In the past 30 years continuous subcutaneous insulin infusion established/introduced as a validate alternative to multiple daily injections. Several trials demonstrated that, when compared to MDI, CSII brings to a better metabolic control, in terms of a reduction of glycated hemoglobin and blood glucose variability, hypoglycemic episodes and improvement in quality of life. Because of their pharmacokinetic and pharmacodynamic characteristics, rapid-action insulin analogues are imposed as best insulin to be used in CSII. The rapid onset and the fast reached peak make them better mimic the way how pancreas secretes insulin. CSII by pump is not free from issues. Catheter occlusions, blockages, clogs can arrest insulin administration. The consequent higher levels of glycemic values, can easily bring to the onset of ketoacidosis, with an high risk for patients' life. Aspart is a rapid analogue obtained by aminoacidic substitution. It is as effective as lispro and glulisine in gaining a good metabolic control and even better in reducing glucose variability. Some studies tried to compare rapid analogues in terms of stability. Obtained data are controversial. An in vivo study evidenced higher stability or glulisine, while studies in vitro highlighted a higher safety of aspart. Nowadays it is not possible to assess which analogues is safer. When the infusion set is changed every 48 hours equivalent rates of occlusions have been observed.

  7. Young people with type 1 diabetes mellitus: Attitudes, perceptions, and experiences of diabetes management and continuous subcutaneous insulin infusion therapy.

    PubMed

    Perry, Lin; James, Steven; Steinbeck, Katharine; Dunbabin, Janet; Lowe, Julia

    2017-06-01

    Continuous subcutaneous insulin infusion (CSII; insulin pump) use is increasing. However, there is little information about how this technology is used compared with other insulin delivery methods (ie, injections) by young people with type 1 diabetes mellitus in Australia. This study explored young people's attitudes, perceptions, and experiences with diabetes management comparing those using with those not using CSII, and proportions likely to transition to adult services requiring initiation and/or support for CSII use. A survey was undertaken of young people (aged 12 to 18 years) with type 1 diabetes mellitus and their parents/guardians living in Hunter New England, Australia, using a questionnaire designed to collect quantitative, descriptive, and demographic data. Most questions were based on previously developed and validated instruments. In total, 107 respondents returned partially or fully completed questionnaires. Respondents had positive attitudes and perceptions of their self-efficacy and diabetes management, but were moderately disturbed by their diabetes and reported experiencing suboptimal management outcomes. Patterns of associations were demonstrated between knowledge, attitudes, and experiences of diabetes modeled by regression analysis. There were no statistically significant differences in responses between users and nonusers of CSII. Over 40% indicated their intention to use the technology as adults. Opportunities for enhanced diabetes service support were clear, and CSII did not appear to be used to its full potential. Service redesign could enhance support for this young population using all preferred insulin delivery methods and should align to patients' goals and preferences to maximize service and patient gain. © 2017 John Wiley & Sons, Ltd.

  8. Continuous 24-h nicotinic acid infusion in rats causes FFA rebound and insulin resistance by altering gene expression and basal lipolysis in adipose tissue.

    PubMed

    Oh, Young Taek; Oh, Ki-Sook; Choi, Yong Min; Jokiaho, Anne; Donovan, Casey; Choi, Sangdun; Kang, Insug; Youn, Jang H

    2011-06-01

    Nicotinic acid (NA) has been used as a lipid drug for five decades. The lipid-lowering effects of NA are attributed to its ability to suppress lipolysis in adipocytes and lower plasma FFA levels. However, plasma FFA levels often rebound during NA treatment, offsetting some of the lipid-lowering effects of NA and/or causing insulin resistance, but the underlying mechanisms are unclear. The present study was designed to determine whether a prolonged, continuous NA infusion in rats produces a FFA rebound and/or insulin resistance. NA infusion rapidly lowered plasma FFA levels (>60%, P < 0.01), and this effect was maintained for ≥5 h. However, when this infusion was extended to 24 h, plasma FFA levels rebounded to the levels of saline-infused control rats. This was not due to a downregulation of NA action, because when the NA infusion was stopped, plasma FFA levels rapidly increased more than twofold (P < 0.01), indicating that basal lipolysis was increased. Microarray analysis revealed many changes in gene expression in adipose tissue, which would contribute to the increase in basal lipolysis. In particular, phosphodiesterase-3B gene expression decreased significantly, which would increase cAMP levels and thus lipolysis. Hyperinsulinemic glucose clamps showed that insulin's action on glucose metabolism was improved during 24-h NA infusion but became impaired with increased plasma FFA levels after cessation of NA infusion. In conclusion, a 24-h continuous NA infusion in rats resulted in an FFA rebound, which appeared to be due to altered gene expression and increased basal lipolysis in adipose tissue. In addition, our data support a previous suggestion that insulin resistance develops as a result of FFA rebound during NA treatment. Thus, the present study provides an animal model and potential molecular mechanisms of FFA rebound and insulin resistance, observed in clinical studies with chronic NA treatment.

  9. Continuous 24-h nicotinic acid infusion in rats causes FFA rebound and insulin resistance by altering gene expression and basal lipolysis in adipose tissue

    PubMed Central

    Oh, Young Taek; Oh, Ki-Sook; Choi, Yong Min; Jokiaho, Anne; Donovan, Casey; Choi, Sangdun; Kang, Insug

    2011-01-01

    Nicotinic acid (NA) has been used as a lipid drug for five decades. The lipid-lowering effects of NA are attributed to its ability to suppress lipolysis in adipocytes and lower plasma FFA levels. However, plasma FFA levels often rebound during NA treatment, offsetting some of the lipid-lowering effects of NA and/or causing insulin resistance, but the underlying mechanisms are unclear. The present study was designed to determine whether a prolonged, continuous NA infusion in rats produces a FFA rebound and/or insulin resistance. NA infusion rapidly lowered plasma FFA levels (>60%, P < 0.01), and this effect was maintained for ≥5 h. However, when this infusion was extended to 24 h, plasma FFA levels rebounded to the levels of saline-infused control rats. This was not due to a downregulation of NA action, because when the NA infusion was stopped, plasma FFA levels rapidly increased more than twofold (P < 0.01), indicating that basal lipolysis was increased. Microarray analysis revealed many changes in gene expression in adipose tissue, which would contribute to the increase in basal lipolysis. In particular, phosphodiesterase-3B gene expression decreased significantly, which would increase cAMP levels and thus lipolysis. Hyperinsulinemic glucose clamps showed that insulin's action on glucose metabolism was improved during 24-h NA infusion but became impaired with increased plasma FFA levels after cessation of NA infusion. In conclusion, a 24-h continuous NA infusion in rats resulted in an FFA rebound, which appeared to be due to altered gene expression and increased basal lipolysis in adipose tissue. In addition, our data support a previous suggestion that insulin resistance develops as a result of FFA rebound during NA treatment. Thus, the present study provides an animal model and potential molecular mechanisms of FFA rebound and insulin resistance, observed in clinical studies with chronic NA treatment. PMID:21386057

  10. Cost-effectiveness of continuous subcutaneous insulin infusion in people with type 2 diabetes in the Netherlands.

    PubMed

    Roze, S; Duteil, E; Smith-Palmer, J; de Portu, S; Valentine, W; de Brouwer, B F E; Reznik, Y; de Valk, H W

    2016-08-01

    Up to 30% of insulin-treated type 2 diabetes patients are unable to achieve HbA1c targets despite optimization of insulin multiple daily injections (MDI). For these patients the use of continuous subcutaneous insulin infusion (CSII) represents a useful but under-utilized alternative. The aim of the present analysis was to examine the cost-effectiveness of initiating CSII in type 2 diabetes patients failing to achieve good glycemic control on MDI in the Netherlands. Long-term projections were made using the IMS CORE Diabetes Model. Clinical input data were sourced from the OpT2mise trial. The analysis was performed over a lifetime time horizon. The discount rates applied to future costs and clinical outcomes were 4% and 1.5% per annum, respectively. CSII was associated with improved quality-adjusted life expectancy compared with MDI (9.38 quality-adjusted life years [QALYs] vs 8.95 QALYs, respectively). The breakdown of costs indicated that ∼50% of costs were attributable to diabetes-related complications. Higher acquisition costs of CSII vs MDI were partially offset by the reduction in complications. The ICER was estimated at EUR 62,895 per QALY gained and EUR 60,474 per QALY gained when indirect costs were included. In the Netherlands, CSII represents a cost-effective option in patients with type 2 diabetes who continue to have poorly-controlled HbA1c despite optimization of MDI. Since the ICER falls below the willingness-to-pay threshold of EUR 80,000 per QALY gained, CSII is likely to represent good-value for money in the treatment of poorly-controlled T2D patients compared with MDI.

  11. Continuous Subcutaneous Insulin Infusion (CSII) Pumps for Type 1 and Type 2 Adult Diabetic Populations: An Evidence-Based Analysis.

    PubMed

    2009-01-01

    In June 2008, the Medical Advisory Secretariat began work on the Diabetes Strategy Evidence Project, an evidence-based review of the literature surrounding strategies for successful management and treatment of diabetes. This project came about when the Health System Strategy Division at the Ministry of Health and Long-Term Care subsequently asked the secretariat to provide an evidentiary platform for the Ministry's newly released Diabetes Strategy.After an initial review of the strategy and consultation with experts, the secretariat identified five key areas in which evidence was needed. Evidence-based analyses have been prepared for each of these five areas: insulin pumps, behavioural interventions, bariatric surgery, home telemonitoring, and community based care. For each area, an economic analysis was completed where appropriate and is described in a separate report.To review these titles within the Diabetes Strategy Evidence series, please visit the Medical Advisory Secretariat Web site, http://www.health.gov.on.ca/english/providers/program/mas/mas_about.html,DIABETES STRATEGY EVIDENCE PLATFORM: Summary of Evidence-Based AnalysesContinuous Subcutaneous Insulin Infusion Pumps for Type 1 and Type 2 Adult Diabetics: An Evidence-Based AnalysisBehavioural Interventions for Type 2 Diabetes: An Evidence-Based AnalysisBARIATRIC SURGERY FOR PEOPLE WITH DIABETES AND MORBID OBESITY: An Evidence-Based SummaryCommunity-Based Care for the Management of Type 2 Diabetes: An Evidence-Based AnalysisHome Telemonitoring for Type 2 Diabetes: An Evidence-Based AnalysisApplication of the Ontario Diabetes Economic Model (ODEM) to Determine the Cost-effectiveness and Budget Impact of Selected Type 2 Diabetes Interventions in Ontario The objective of this analysis is to review the efficacy of continuous subcutaneous insulin infusion (CSII) pumps as compared to multiple daily injections (MDI) for the type 1 and type 2 adult diabetics. Insulin therapy is an integral component of the

  12. Designing the modern pump: engineering aspects of continuous subcutaneous insulin infusion software.

    PubMed

    Welsh, John B; Vargas, Steven; Williams, Gary; Moberg, Sheldon

    2010-06-01

    Insulin delivery systems attracted the efforts of biological, mechanical, electrical, and software engineers well before they were commercially viable. The introduction of the first commercial insulin pump in 1983 represents an enduring milestone in the history of diabetes management. Since then, pumps have become much more than motorized syringes and have assumed a central role in diabetes management by housing data on insulin delivery and glucose readings, assisting in bolus estimation, and interfacing smoothly with humans and compatible devices. Ensuring the integrity of the embedded software that controls these devices is critical to patient safety and regulatory compliance. As pumps and related devices evolve, software engineers will face challenges and opportunities in designing pumps that are safe, reliable, and feature-rich. The pumps and related systems must also satisfy end users, healthcare providers, and regulatory authorities. In particular, pumps that are combined with glucose sensors and appropriate algorithms will provide the basis for increasingly safe and precise automated insulin delivery-essential steps to developing a fully closed-loop system.

  13. Continuous intraperitoneal insulin infusion in type 1 diabetes: a 6-year post-trial follow-up.

    PubMed

    van Dijk, Peter R; Logtenberg, Susan J J; Groenier, Klaas H; Gans, Rijk O B; Kleefstra, Nanne; Bilo, Henk Jg

    2014-04-07

    Continuous intraperitoneal insulin infusion (CIPII) with an implantable pump is a treatment option for patients with type 1 diabetes mellitus (T1DM). Aim of the present study was to describe the long-term course of glycaemic control, complications, health related quality of life (HRQOL) and treatment satisfaction among T1DM patients treated with CIPII. Nineteen patients that participated in a randomized cross-over trial comparing CIPII and subcutaneous (SC) therapy in 2006 were followed until 2012. Laboratory, continuous glucose monitoring, HRQOL and treatment satisfaction measurements were performed at the start of the study, the end of the SC-, the end of the CIPII treatment phase in 2006 and during CIPII therapy in 2012. Linear mixed models were used to calculate estimated values and to test differences between the moments in time. In 2012, more time was spent in hyperglycaemia than after the CIPII treatment phase in 2006: 37% (95% CI 29, 44) vs. 55% (95% CI 48, 63), mean difference 19.8% (95% CI 3.0, 36.6). HbA1c was 65 mmol/mol (95% CI 60, 71) at the end of the SC treatment phase in 2006, 58 mmol/mol (95% CI 53, 64) at the end of the CIPII treatment phase and 65 mmol/mol (95% CI 60, 71) in 2012, respectively (p > 0.05). In 2012, the median number of grade 2 hypoglycaemic events per week (1 (95% CI 0, 2)) was still significantly lower than during prior SC therapy (3 (95% CI 2, 4)): mean change -1.8 (95% CI -3.4, -0.4). Treatment satisfaction with CIPII was better than with SC insulin therapy and HRQOL remained stable. Pump or catheter dysfunction of the necessitated re-operation in 7 patients. No mortality was reported. After 6 years of CIPII treatment, glycaemic regulation is stable and the number of hypoglycaemic events decreased compared to SC insulin therapy. Treatment satisfaction with CIPII is superior to SC insulin therapy, HRQOL is stable and complications are scarce. CIPII is a safe and effective treatment option for selected patients with T1DM

  14. Continuous subcutaneous insulin infusion vs intensive conventional insulin therapy in pregnant diabetic women: a systematic review and metaanalysis of randomized, controlled trials.

    PubMed

    Mukhopadhyay, Asima; Farrell, Tom; Fraser, Robert B; Ola, Bolarinde

    2007-11-01

    The objective of the study was to study the effects of continuous subcutaneous insulin infusion (CSII) vs multiple-dose insulin (MDI) therapy on glycemic control and pregnancy outcome in diabetic women. Randomized, controlled trials comparing CSII vs MDI in pregnant diabetic women were included after an electronic database search. Studies were rated for quality independently by 2 reviewers in accordance with the Quality of Reporting of Metaanalyses statement. Summary weighted mean difference and odds ratio were estimated for insulin dose, birthweight, gestational age, mode of delivery, hypoglycemic/ketotic episodes, worsening retinopathy, neonatal hypoglycemia, and rates of intrauterine fetal death. Six randomized clinical trials met the inclusion criteria. Pregnancy outcomes and glycemic control were not significantly different among treatment groups. Higher number of ketoacidotic episodes and diabetic retinopathy found in the CSII group did not reach statistical significance. This systematic review does not show any advantage or disadvantage of using CSII over MDI in pregnant diabetic women. Large multicenter, randomized, controlled trials addressing the quality of life/cost effectiveness are required.

  15. Continuous Subcutaneous Insulin Infusion in Children: A Pilot Study Validating a Protocol to Avoid Hypoglycemia at Initiation.

    PubMed

    Manousaki, Despoina; Deladoëy, Johnny; Geoffroy, Louis; Olivier, Patricia

    2017-01-01

    The occurrence of hypoglycemia and hyperglycemia during the first days after transition to continuous subcutaneous insulin infusion (CSII) in patients with type 1 diabetes has not been systematically studied in children. The aim of this prospective study was to demonstrate that the protocol applied in our diabetes clinic is safe at CSII initiation in children. We assessed 22 pediatric patients with type 1 diabetes, using continuous glucose monitoring (CGM) before and after CSII initiation (±3 days). After CSII initiation, there was no difference in the rates of hypoglycemic events expressed as relative rates (RRs) per person-reading (RR = 0.85, p = 0.52, 95% CI 0.52-1.39), as well as in the number of prolonged hypoglycemic events (>1 h) per day (RR = 1.12, p = 0.56, 95% CI 0.75-1.68). We observed only a trend toward prolonged episodes of hyperglycemia after pump initiation (RR = 1.52, p = 0.06, 95% CI 0.97-2.35). Our study is the first to assess, through CGM and in a prospective way, the impact of a CSII initiation protocol on glycemic values. Our protocol provides a safe model to avoid hypoglycemia at CSII initiation in children. www.ClinicalTrials.gov, identifier NCT01840358.

  16. Epidemiological characterization of diabetic patients on therapy with continuous subcutaneous insulin infusion and continuous glucose monitoring in real time.

    PubMed

    Aristizábal, Natalia; Ramírez, Alex; Hincapié-García, Jaime; Laiton, Estefany; Aristizábal, Carolina; Cuesta, Diana; Monsalve, Claudia; Hincapié, Gloria; Zapata, Eliana; Abad, Verónica; Delgado, Maria-Rocio; Torres, José-Luis; Palacio, Andrés; Botero, José

    2015-11-01

    To describe baseline characteristics of diabetic patients who were started on insulin pump and real time continuous glucose monitor (CSII-rtCGM) in a specialized center in Medellin, Colombia. All patients with diabetes with complete data who were started on CSII-rtCGM between February 2010 and May 2014 were included. This is a descriptive analysis of the sociodemographic and clinical characteristics. 141 of 174 patients attending the clinic were included. 90,1% had type 1diabetes (T1D). The average age of T1D patients at the beginning of therapy was 31,4 years (SD 14,1). 75.8% of patients had normal weight (BMI<25), 21.0% were overweight (BMI 25-30) and 2,3% were obese (BMI>30). The median duration of T1D was 13 years (P25-P75=10.7-22.0). 14,2% of the patients were admitted at least once in the year preceding the start of CSII-rtCGM because of diabetes related complications. Mean A1c was 8.6%±1.46%. The main reasons for starting CSII-rtCGM were: poor glycemic control (50.2%); frequent hypoglycemia, nocturnal hypoglycemia, hypoglycemia related to exercise, asymptomatic hypoglycemia (30.2%); severe hypoglycemia (16.44%) and dawn phenomena (3.1%). Baseline characteristics of patients included in this study who were started on CSII-rtCGM are similar to those reported in the literature. The Clinic starts CSII-rtCGM mainly in T1D patients with poor glycemic control, frequent or severe hypoglycemia despite being on basal/bolus therapy. Copyright © 2015 SEEN. Published by Elsevier España, S.L.U. All rights reserved.

  17. Circadian hormone profiles and insulin sensitivity in patients with Addison's disease: a comparison of continuous subcutaneous hydrocortisone infusion with conventional glucocorticoid replacement therapy.

    PubMed

    Björnsdottir, Sigridur; Øksnes, Marianne; Isaksson, Magnus; Methlie, Paal; Nilsen, Roy M; Hustad, Steinar; Kämpe, Olle; Hulting, Anna-Lena; Husebye, Eystein S; Løvås, Kristian; Nyström, Thomas; Bensing, Sophie

    2015-07-01

    Conventional glucocorticoid replacement therapy in patients with Addison's disease (AD) is unphysiological with possible adverse effects on mortality, morbidity and quality of life. The diurnal cortisol profile can likely be restored by continuous subcutaneous hydrocortisone infusion (CSHI). The aim of this study was to compare circadian hormone rhythms and insulin sensitivity in conventional thrice-daily regimen of glucocorticoid replacement therapy with CSHI treatment in patients with AD. An open, randomized, two-period, 12-week crossover multicentre trial in Norway and Sweden. Ten Norwegian patients were admitted for 24-h sampling of hormone profiles. Fifteen Swedish patients underwent euglycaemic-hyperinsulinaemic clamp. Thrice-daily regimen of oral hydrocortisone (OHC) and CSHI treatment. We measured the circadian rhythm of cortisol, adrenocorticotropic hormone (ACTH), growth hormone (GH), insulin-like growth factor-1, (IGF-1), IGF-binding protein-3 (IGFBP-3), glucose, insulin and triglycerides during OHC and CSHI treatment. Euglycaemic-hyperinsulinaemic clamp was used to assess insulin sensitivity. Continuous subcutaneous hydrocortisone infusion provided a more physiological circadian cortisol curve including a late-night cortisol surge. ACTH levels showed a near normal circadian variation for CSHI. CSHI prevented a continuous decrease in glucose during the night. No difference in insulin sensitivity was observed between the two treatment arms. Continuous subcutaneous hydrocortisone infusion replacement re-established a circadian cortisol rhythm and normalized the ACTH levels. Patients with CSHI replacement had a more stable night-time glucose level compared with OHC without compromising insulin sensitivity. Thus, restoring night-time cortisol levels might be advantageous for patients with AD. © 2015 John Wiley & Sons Ltd.

  18. Use and Effectiveness of Continuous Subcutaneous Insulin Infusion (CSII) and Multiple Daily Insulin Injection Therapy (MIT) in Children, Adolescents and Young Adults with Type 1 Diabetes Mellitus.

    PubMed

    Schiel, R; Burgard, D; Perenthaler, T; Stein, G; Kramer, G; Steveling, A

    2016-02-01

    Today continuous subcutaneous insulin infusion (CSII) is frequently used in children and adolescents with type 1 diabetes mellitus. The present cross-sectional trial aimed to document current practice, quality of diabetes control and incidence of acute complications in different age-groups under CSII vs. multiple daily insulin injection therapy (MIT). Moreover the survey analyzed socio-demographic backgrounds of the patients. A total of 901 patients (age 11.5±4.0, diabetes duration 4.0±3.6 years) was entered in the database. Clinical data, laboratory parameters and, using a standardized questionnaire, socio-demographic data were assessed. For age-related analyses patients were allocated to 4 groups: pre-school children (< 6 years), pre-adolescents (≥ 6 and<11 years), adolescents (≥ 11 and<16 years) and young adults (≥ 16 and<22 years). Of the cohort n=194 had a CSII, n=707 had a MIT. Patients with CSII vs. MIT had a longer diabetes duration, they used more frequently insulin analogues, performed more frequently blood-glucose self-tests and had a lower insulin dosage per kilogram body weight. In respect of HbA1c, the mean amplitude of blood-glucose excursions, but also of lipids, creatinine, microalbuminuria and blood pressure, there were no differences in neither age-group between patients with CSII and MIT. In patients with CSII and MIT, there was a tendency (p<0.05) towards an increase in HbA1c in adolescents and young adults and there was a decrease (p<0.05 for tendency) in the frequency of hypoglycaemia from the age group of young adults to pre-school children. Adolescents and young adults with CSII had a higher educational level. Pre-adolescents, adolescents and young adults with CSII have also better diabetes-related knowledge. Moreover, in all age-groups, the parents of patients with CSII had mostly a lower unemployment rate and higher educational levels. The present analyses demonstrate that in all age-groups CSII provides convenient and

  19. [Continuous-infusion ketamine].

    PubMed

    Mancini, P G; Caggese, G; Di Fabio, A; Di Nino, G F; Cocchi, V

    1980-08-01

    An investigation was made of the employment of ketamin as the sole anaesthetic in general surgery, using continuous infusion of a 1% solution for both induction and maintenance in 118 cases. ECG was monitored and arterial pressure was measured invasively. Central venous pressure was also determined in 10 cases. Changes in serum enzyme values during and after surgery were examined in 35 patients. Blood samples were withdrawn before induction, after the return to consciousness, and 24 hr after the operation. Side-effects were common, but slight. Five patients suffered from nightmares, but these were persons with marked imaginative activity and a melancholic nature. Cardiocirculatory function was satisfactory. In particular, peripheral perfusion was excellent in all cases.

  20. Cost-effectiveness of continuous subcutaneous insulin infusion versus multiple daily injections of insulin in Type 1 diabetes: a systematic review.

    PubMed

    Roze, S; Smith-Palmer, J; Valentine, W; de Portu, S; Nørgaard, K; Pickup, J C

    2015-11-01

    Continuous subcutaneous insulin infusion (CSII) is increasingly used in clinical practice for the management of selected patients with Type 1 diabetes. Several cost-effectiveness studies comparing CSII vs. multiple insulin injections (MDI) have been reported. The aim was systematically to review these analyses and test the hypothesis that CSII is a cost-effective use of healthcare resources across settings. A literature review was performed using MEDLINE, Cochrane Library and other databases. No time limit or language restrictions were applied. After two rounds of screening, 11 cost-effectiveness analyses were included in the final review, of which nine used the CORE Diabetes Model. A narrative synthesis was conducted and mean cost effectiveness calculated. CSII was considered cost-effective vs. MDI in Type 1 diabetes in all 11 studies in 8 countries, with a mean (95% CI) incremental cost effectiveness ratio of €30 862 (17 997-43 727), US$40 143 (23 409-56 876) per quality-adjusted life year (QALY) gained. CSII was associated with improved life expectancy and quality-adjusted life expectancy (0.4-1.1 QALYs in adults), driven by lower HbA(1c) and lower frequency of hypoglycaemic events vs. MDI. CSII was associated with higher lifetime direct costs due to higher treatment costs but this was partially offset by cost-savings from reduced diabetes-related complications. Published cost-effectiveness analyses show that in Type 1 diabetes CSII is cost-effective vs. MDI across a number of settings for patients who have poor glycaemic control and/or problematic hypoglycaemia on MDI, with cost-effectiveness highly sensitive to the reduction in HbA1c and hypoglycaemia frequency associated with CSII. © 2015 The Authors. Diabetic Medicine © 2015 Diabetes UK.

  1. Type 1 diabetes control and pregnancy outcomes in women treated with continuous subcutaneous insulin infusion (CSII) or with insulin glargine and multiple daily injections of rapid-acting insulin analogues (glargine-MDI).

    PubMed

    Bruttomesso, D; Bonomo, M; Costa, S; Dal Pos, M; Di Cianni, G; Pellicano, F; Vitacolonna, E; Dodesini, A R; Tonutti, L; Lapolla, A; Di Benedetto, A; Torlone, E

    2011-11-01

    The best way to treat pregnant patients who have type 1 diabetes is still unclear. For this reason, the present study compared metabolic control and maternal-fetal outcomes in patients treated with continuous subcutaneous infusions of rapid-acting insulin analogues (CSII) or with insulin glargine and multiple daily injections of rapid-acting insulin analogues (glargine-MDI). This retrospective multicentre study involved 144 women with type 1 diabetes, 100 of whom were using CSII and 44 glargine-MDI. Outcomes analyzed were metabolic control, diabetes complications, pregnancy outcome, perinatal morbidity and mortality, and fetal malformations. The two groups were comparable for age, prepregnancy BMI, primiparous rate and diabetes complications, although patients using CSII had longer duration of diabetes (P=0.03) and higher White classifications (P=0.04). In both groups, metabolic control improved during pregnancy, but good control was reached earlier among patients using CSII. At parturition, patients using CSII had lower HbA(1c) (6.2±0.7% vs 6.5±0.8%; P=0.02) and required less insulin (P<0.01). Weight gain was similar in both groups, and maternal-fetal outcomes did not differ. In pregnant patients with type 1 diabetes, MDI and CSII are equivalent in terms of metabolic control and fetal-maternal outcomes, although patients using CSII achieved good control earlier and with less insulin. Copyright © 2011 Elsevier Masson SAS. All rights reserved.

  2. Improved Postprandial Glycemic Control with Faster-Acting Insulin Aspart in Patients with Type 1 Diabetes Using Continuous Subcutaneous Insulin Infusion

    PubMed Central

    Johnson, Joseph A.; Hyveled, Liselotte; Tamer, Søren C.; Demissie, Marek

    2017-01-01

    Abstract Background: Faster aspart is insulin aspart (IAsp) in a new formulation, which in continuous subcutaneous insulin infusion (CSII) in subjects with type 1 diabetes has shown a faster onset and offset of glucose-lowering effect than IAsp. Methods: This double-blind, randomized, crossover active-controlled trial compared 2-h postprandial plasma glucose (PPG) response, following 2 weeks of CSII with faster aspart or IAsp. Primary endpoint: mean change in PPG 2 h after a standardized meal test (ΔPGav,0–2h). Subjects (n = 43) had masked continuous glucose monitoring (CGM) throughout. Results: Faster aspart provided a statistically significantly greater glucose-lowering effect following the meal versus IAsp: ΔPGav,0–2h: 3.03 mmol/L versus 4.02 mmol/L (54.68 mg/dL vs. 72.52 mg/dL); estimated treatment difference (ETD) [95% CI]: −0.99 mmol/L [–1.95; −0.03] (−17.84 mg/dL [–35.21; −0.46]; P = 0.044). One hour postmeal, PG levels were −1.64 mmol/L (−29.47 mg/dL) lower with faster aspart versus IAsp (P = 0.006). Interstitial glucose (IG) profiles supported these findings; the largest differences were observed at breakfast: 9.08 versus 9.56 mmol/L (163.57 vs. 172.19 mg/dL; ETD [95% CI]: −0.48 mmol/L [–0.97; 0.01]; −8.62 mg/dL [–17.49; 0.24]; P = 0.057). Duration of low IG levels (≤3.9 mmol/L [70 mg/dL] per 24 h) was statistically significantly shorter for faster aspart versus IAsp (2.03 h vs. 2.45 h; ETD [95% CI]: −0.42 [–0.72; −0.11]; P = 0.008). No unexpected safety findings were observed. Conclusions: CSII delivery of faster aspart had a greater glucose-lowering effect than IAsp after a meal test. CGM results recorded throughout all meals supported this finding, with less time spent with low IG levels. PMID:28055230

  3. Improved Postprandial Glycemic Control with Faster-Acting Insulin Aspart in Patients with Type 1 Diabetes Using Continuous Subcutaneous Insulin Infusion.

    PubMed

    Bode, Bruce W; Johnson, Joseph A; Hyveled, Liselotte; Tamer, Søren C; Demissie, Marek

    2017-01-01

    Faster aspart is insulin aspart (IAsp) in a new formulation, which in continuous subcutaneous insulin infusion (CSII) in subjects with type 1 diabetes has shown a faster onset and offset of glucose-lowering effect than IAsp. This double-blind, randomized, crossover active-controlled trial compared 2-h postprandial plasma glucose (PPG) response, following 2 weeks of CSII with faster aspart or IAsp. Primary endpoint: mean change in PPG 2 h after a standardized meal test (ΔPGav,0-2h). Subjects (n = 43) had masked continuous glucose monitoring (CGM) throughout. Faster aspart provided a statistically significantly greater glucose-lowering effect following the meal versus IAsp: ΔPGav,0-2h: 3.03 mmol/L versus 4.02 mmol/L (54.68 mg/dL vs. 72.52 mg/dL); estimated treatment difference (ETD) [95% CI]: -0.99 mmol/L [-1.95; -0.03] (-17.84 mg/dL [-35.21; -0.46]; P = 0.044). One hour postmeal, PG levels were -1.64 mmol/L (-29.47 mg/dL) lower with faster aspart versus IAsp (P = 0.006). Interstitial glucose (IG) profiles supported these findings; the largest differences were observed at breakfast: 9.08 versus 9.56 mmol/L (163.57 vs. 172.19 mg/dL; ETD [95% CI]: -0.48 mmol/L [-0.97; 0.01]; -8.62 mg/dL [-17.49; 0.24]; P = 0.057). Duration of low IG levels (≤3.9 mmol/L [70 mg/dL] per 24 h) was statistically significantly shorter for faster aspart versus IAsp (2.03 h vs. 2.45 h; ETD [95% CI]: -0.42 [-0.72; -0.11]; P = 0.008). No unexpected safety findings were observed. CSII delivery of faster aspart had a greater glucose-lowering effect than IAsp after a meal test. CGM results recorded throughout all meals supported this finding, with less time spent with low IG levels.

  4. Use of Microdialysis-Based Continuous Glucose Monitoring to Drive Real-Time Semi-Closed-Loop Insulin Infusion

    PubMed Central

    Freckmann, Guido; Jendrike, Nina; Buck, Harvey; Bousamra, Steven; Galley, Paul; Thukral, Ajay; Wagner, Robin; Weinert, Stefan; Haug, Cornelia

    2014-01-01

    Continuous glucose monitoring (CGM) and automated insulin delivery may make diabetes management substantially easier, if the quality of the resulting therapy remains adequate. In this study, a semi-closed-loop control algorithm was used to drive insulin therapy and its quality was compared to that of subject-directed therapy. Twelve subjects stayed at the study site for approximately 70 hours and were provided with the investigational Automated Pancreas System Test Stand (APS-TS), which was used to calculate insulin dosage recommendations automatically. These recommendations were based on microdialysis CGM values and common diabetes therapy parameters. For the first half of their stay, the subjects directed their diabetes therapy themselves, whereas for the second half, the insulin recommendations were delivered by the APS-TS (so-called algorithm-driven therapy). During subject-directed therapy, the mean glucose was 114 mg/dl compared to 125 mg/dl during algorithm-driven therapy. Time in target (90 to 150 mg/dl) was approximately 46% during subject-directed therapy and approximately 58% during algorithm-driven therapy. When subjects directed their therapy, approximately 2 times more hypoglycemia interventions (oral administration of carbohydrates) were required than during algorithm-driven therapy. No hyperglycemia interventions (delivery of addition insulin) were necessary during subject-directed therapy, while during algorithm-driven therapy, 2 hyperglycemia interventions were necessary. The APS-TS was able to adequately control glucose concentrations in the subjects. Time in target was at least comparable or moderately higher during closed-loop control and markedly fewer hypoglycemia interventions were required, thus increasing patient safety. PMID:25205589

  5. Comparison of high-dose and low-dose insulin by continuous intravenous infusion in the treatment of diabetic ketoacidosis in children.

    PubMed

    Burghen, G A; Etteldorf, J N; Fisher, J N; Kitabchi, A Q

    1980-01-01

    We studied the efficacy of low-dose (0.1 U/kg/h) and high-dose (1..0 U/kg/h) insulin, given randomly to children with diabetic ketoacidosis (DKA) by continuous intravenous infusion without a loading dose. Plasma glucose reached 250 mg/dl in 3.4 +/- 0.4 h with the high-dose insulin group compared with 5.4 +/- 0.5 h with the low-dose insulin group (P < 0.01). During the first 12 h of therapy, plasma glucose fell below 100 mg/dl in 2 of 16 in the low-dose compared with 12 of 16 in the high-dose patients. The decrement of ketone bodies, cortisol, and glucagon was similar in both groups. The number of hours required for HCO3(-) greater than or equal to meq/l and arterial blood pH greater than or equal to 7.30 were not significantly different in the two groups. Hypokalemia (K < 3.4 meq/L) occurred in 3 of 16 low-dose and 10 of 16 high-dose patients. The data show that low-dose insulin, with a slower rate of glucose decrease, is as effective as a high dose for the treatment of DKA in children with less incidence of hypokalemia and decreased potential for hypoglycemia.

  6. Effect of one year continuous subcutaneous infusion of a somatostatin analogue, octreotide, on early retinopathy, metabolic control and thyroid function in Type I (insulin-dependent) diabetes mellitus.

    PubMed

    Kirkegaard, C; Nørgaard, K; Snorgaard, O; Bek, T; Larsen, M; Lund-Andersen, H

    1990-06-01

    Growth hormone is assumed to be involved in the development of diabetic retinopathy. In a randomized study we evaluated the possible effects of one year treatment with a somatostatin (SRIH) analogue, octreotide, on early retinopathy and on metabolism in Type I (insulin-dependent) diabetes mellitus. Eleven patients were allocated to treatment with a continuous sc infusion of 400 micrograms octreotide per day and 9 served as controls. Only 7 patients from each group completed the study. Three octreotide-treated patients left the study owing to severe diarrhea. The subjects were evaluated at entry, after 2, 6 and 12 months treatment, and 2 months after withdrawal. Octreotide induced a decrease in GH secretion, expressed as the area under the 24 h serum GH profiles (p less than 0.05), and of the serum levels of IGF-I (p less than 0.05). The entire decline in GH levels occurred during the daytime, whereas the nocturnal levels were unaffected. Retinopathy, as assessed by determination of the blood retina barrier permeability, by colour fundus photography, and flurescein angiography was unchanged in both groups. Apart from a decline in insulin requirements, octreotide had no major effect on glycemic control, but induced a mild transient pituitary hypothyroidism, not clinically relevant. We conclude that treatment with octreotide for one year has modest effects on GH, IGF-I, and glucose metabolism, but has no significant effect on early retinopathy in Type I (insulin-dependent) diabetes.

  7. Continuous Subcutaneous Insulin Infusion During Pregnancy in Women with Complicated Type 1 Diabetes Is Associated with Better Glycemic Control but Not with Improvement in Pregnancy Outcomes.

    PubMed

    Kekäläinen, Päivi; Juuti, Mari; Walle, Tiina; Laatikainen, Tiina

    2016-03-01

    The aim of this study was to evaluate maternal and fetal pregnancy outcomes of women with type 1 diabetes managed on continuous subcutaneous insulin infusion (CSII) compared with multiple daily insulin injections (MDI). Pregnancy outcomes were assessed retrospectively in women with type 1 diabetes who were patients of the Diabetes Clinic of North Karelia Hospital (Joensuu, Finland) between 2000 and 2012. The medical records of 72 women experiencing 135 pregnancies and data of their infants were retrospectively reviewed. In total, 48 pregnancies were treated with CSII and 87 with MDI. Women on CSII treatment were older and had more diabetes complications compared with women on MDI. No significant differences in glycated hemoglobin (HbA1c) levels were observed between the CSII and MDI groups before or during pregnancy. Maternal or fetal outcomes did not differ between the treatment groups. However, among women with complicated diabetes, HbA1c levels were significantly lower in the CSII group until the second trimester (prepregnancy, 7.22% vs. 8.14%, respectively [P = 0.034]; first trimester, 6.85% vs. 7.87% [P < 0.001]; second trimester, 6.41% vs. 7.03% [P = 0.029]) without an increased rate of maternal hypoglycemia. Pregnancy outcomes were similar regardless of insulin treatment modality. Although using an insulin pump did not result in improvement of pregnancy outcomes, it allowed for better glycemic control in pregnancies of women with complicated diabetes. Therefore, it is worth considering in high-risk T1DM pregnancies, especially if good glycemic control is not achieved otherwise.

  8. SAFETY AND EFFICACY OF A PERI-OPERATIVE PROTOCOL FOR PATIENTS WITH DIABETES TREATED WITH CONTINUOUS SUBCUTANEOUS INSULIN INFUSION WHO ARE ADMITTED FOR SAME-DAY SURGERY.

    PubMed

    Sobel, Sandra I; Augustine, Marilyn; Donihi, Amy C; Reider, Jodie; Forte, Patrick; Korytkowski, Mary

    2015-11-01

    The number of people with diabetes using continuous subcutaneous insulin infusions (CSII) with an insulin pump has risen dramatically, creating new challenges when these patients are admitted to the hospital for surgical or other procedures. There is limited literature guiding CSII use during surgical procedures. The study was carried out in a large, urban, tertiary care hospital. We enrolled 49 patients using insulin pump therapy presenting for 57 elective surgeries. We developed a CSII peri-operative glycemic management protocol (PGMP) to standardize insulin pump management in patients admitted to a same-day surgery unit (SDSU). The purpose was evaluate the safety (% capillary blood glucose (CBG) <70 mg/dL and/or pump incidents) and efficacy (first postoperative CBG ≤200 mg/dL) of the CSII PGMP. We determine the contribution of admission CBG, type of anesthesia, surgery length, and peri-operative steroid use on postoperative glycemic control. Overall, 63% of patients treated according to the CSII PGMP had a first postoperative CBG ≤200 mg/dL. There were no episodes of intra- or postoperative hypoglycemia. For patients treated with the CSII PGMP, the mean postoperative CBG was lower in patients with anticipated or actual surgical length ≤120 minutes (158.1 ± 53.9 vs. 216 ± 77.7 mg/dL, P<.01). No differences were observed with admission CBG, type of anesthesia, or steroid use. This study demonstrates that a CSII PGMP is both safe and effective for patients admitted for elective surgical procedures and provides an example of a standardized protocol for use in clinical practice.

  9. Report of a 7 year case-control study of continuous intraperitoneal insulin infusion and subcutaneous insulin therapy among patients with poorly controlled type 1 diabetes mellitus: favourable effects on hypoglycaemic episodes.

    PubMed

    van Dijk, P R; Logtenberg, S J J; Groenier, K H; Gans, R O B; Bilo, H J G; Kleefstra, N

    2014-11-01

    Continuous intraperitoneal insulin infusion (CIPII) is a last-resort treatment option for patients with type 1 diabetes mellitus (T1DM) who fail to reach adequate glycaemic control with subcutaneous (SC) insulin therapy. Aim was to compare the long-term effects of CIPII and SC insulin therapy among patients with T1DM in poor glycaemic control. Patients in which CIPII was initiated in 2006 were compared with a control group of T1DM patients who continued SC therapy. Linear mixed models were used to calculate differences between the baseline (2006) and final (2013) measurements within and between groups. A total of 95 patients of which 21 were using CIPII and 74 using SC insulin were included. Within the CIPII group, the number of hypoglycaemic episodes decreased with -5 (95% CI -8 to -3) per 2 weeks while it remained stable among SC patients. Over time, only the number of hypoglycaemic episodes decreased more with CIPII as compared to SC insulin treatment (difference: -6 (95% CI -9 to -4)). There were no differences between treatment groups regarding clinical parameters and quality of life scores over time. Pump or catheter dysfunction led to ketoacidosis in 6 patients: 2 using CIPII and 4 SC insulin. After 7 years of follow-up, there is a persistent decline of hypoglycaemic events among CIPII treated T1DM patients. Besides less hypoglycaemic episodes with CIPII therapy, there are no differences between long-term CIPII and SC insulin therapy. Copyright © 2014 Elsevier Ireland Ltd. All rights reserved.

  10. Budget impact of continuous subcutaneous insulin infusion therapy in patients with type 1 diabetes who experience severe recurrent hypoglycemic episodes in Spain.

    PubMed

    Giménez, Marga; Elías, Isabel; Álvarez, María; Quirós, Carmen; Conget, Ignacio

    Hypoglycemia is one of the most common complications to achieve a good metabolic control, and has been listed by several scientific associations as a common indication to start treatment with continuous subcutaneous insulin infusion (CSII). Use of CSII is still residual in Spain as compared to neighbouring countries, and cost of acquisition cost is one of the main reasons. This study estimates the budget impact of treatment with CSII, as compared to multiple daily insulin injections, of patients with type 1 diabetes mellitus who experience recurrent severe hypoglycemia episodes from the National Healthcare System perspective. Budget impact was based on a retrospective, observational study evaluating the efficacy of CSII in patients with type 1 diabetes mellitus conducted at Hospital Clínic i Universitari in Barcelona, where one of the main indications for switching to CSII were recurrent severe hypoglycemia episodes. The mean number of annual episodes was 1.33 in the two years prior to CSII start and 0.08 in the last two years of follow up (p=0.003). Costs of treatment and major hypoglycemic events over a four-year period were considered. Costs were taken from different Spanish data sources and expressed in € of 2016. Treatment with CSII increased costs by €9,509 per patient as compared to multiple daily insulin injections (€11,902-€2,393). Cost associated to severe hypoglycemic events decreased by €19,330 per patient treated with CSIII (€1,371-€20,701). Results suggest mean total savings of €9,821 per patient during the four-year study period. The higher costs associated to CSII therapy may be totally offset by the severe hypoglycemic events prevented. Copyright © 2017 SEEN y SED. Publicado por Elsevier España, S.L.U. All rights reserved.

  11. A comparison study of continuous insulin infusion protocols in the medical intensive care unit: computer-guided vs. standard column-based algorithms.

    PubMed

    Newton, Christopher A; Smiley, Dawn; Bode, Bruce W; Kitabchi, Abbas E; Davidson, Paul C; Jacobs, Sol; Steed, R Dennis; Stentz, Frankie; Peng, Limin; Mulligan, Patrick; Freire, Amado X; Temponi, Angel; Umpierrez, Guillermo E

    2010-10-01

    To compare the safety and efficacy of continuous insulin infusion (CII) via a computer-guided and a standard paper form protocol in a medical intensive care unit (ICU). Multicenter randomized trial of 153 ICU patients randomized to CII using the Glucommander (n = 77) or a standard paper protocol (n = 76). Both protocols used glulisine insulin and targeted blood glucose (BG) between 80 mg/dL and 120 mg/dL. The Glucommander resulted in a lower mean BG value (103 ± 8.8 mg/dL vs. 117 ± 16.5 mg/dL, P < 0.001) and in a shorter time to reach BG target (4.8 ± 2.8 vs.7.8 hours ± 9.1 hours, P < 0.01), and once at target resulted in a higher percentage of BG readings within target (71.0 ± 17.0% vs. 51.3 ± 19.7%, P < 0.001) than the standard protocol. Mean insulin infusion rate in the Glucommander was similar to the standard protocol (P = 0.12). The percentages of patients with ≥1 episode of BG <40 mg/dL and <60 mg/dL were 3.9% and 42.9% in the Glucommander and 5.6% and 31.9% in the standard, respectively [P = not significant (NS)]. Repeated measures analyses show that the probabilities of BG reading <40 mg/dL or <60 mg/dL were not significantly different between groups (P = 0.969, P = 0.084) after accounting for within-patient correlations with or without adjusting for time effect. There were no differences between groups in the length of hospital stay (P = 0.704), ICU stay (P = 0.145), or inhospital mortality (P = 0.561). Both treatment algorithms resulted in significant improvement in glycemic control in critically ill patients in the medical ICU. The computer-based algorithm resulted in tighter glycemic control without an increased risk of hypoglycemic events compared to the standard paper protocol.

  12. Effect of flow rate and insulin priming on the recovery of insulin from microbore infusion tubing.

    PubMed

    Fuloria, M; Friedberg, M A; DuRant, R H; Aschner, J L

    1998-12-01

    A retrospective medical record review of 13 consecutive, hyperglycemic, extremely low birth weight (ELBW) infants treated with continuous insulin infusions revealed a 14- to 24-hour delay (mean, 19 hours) in blood glucose normalization despite stepwise increases in insulin infusion rates. This in vitro study examined the effects of flow rate and insulin priming on insulin recovery from polyvinyl chloride (PVC) tubing and polyethylene (PE)-lined PVC tubing infused with a standard insulin stock solution. Stock insulin solution (0.2 U/mL) was infused through microbore PVC or PE-lined tubing at flow rates of 0.05 and 0.2 mL/h. To determine if saturation of nonspecific binding sites would alter effluent insulin concentration, we compared insulin recovery from tubing previously flushed with the stock solution and tubing primed with 5 U/mL of insulin for 20 minutes. Effluent samples, which were collected at baseline and at six time points during a 24-hour period, were immediately frozen at -20 degreesC. Insulin concentration was measured by IMx immunoassay. Data were analyzed using general linear modeling with repeated measures. At 0.05 mL/h flow rate, insulin recovery from unprimed PVC tubing at 1, 2, 4, and 8 hours was 17%, 11%, 27%, and 55%, respectively, with 100% recovery at 24 hours. From insulin-primed tubing, insulin recovery was approximately 70% at 1, 2, and 4 hours, and close to 100% at 8 hours. At a faster flow rate of 0.2 mL/h, insulin recovery at 1, 2, 4, and 8 hours was 22%, 38%, 67%, and 75% vs 42%, 85%, 91% and 95% from unprimed and insulin-primed PVC tubing, respectively. Similar results were obtained from unprimed and insulin-primed PE-lined tubing at 0.2 mL/h flow rate. Priming of microbore tubing with 5 U/mL of insulin solution for 20 minutes to block nonspecific binding sites enhances delivery of a standard insulin stock at infusion rates typically used to treat hyperglycemic ELBW infants. We conclude that priming the tubing with a higher

  13. A multicentre randomized controlled trial of an empowerment-inspired intervention for adolescents starting continuous subcutaneous insulin infusion--a study protocol.

    PubMed

    Brorsson, Anna Lena; Leksell, Janeth; Viklund, Gunnel; Lindholm Olinder, Anna

    2013-12-20

    Continuous subcutaneous insulin infusion (CSII) treatment among children with type 1 diabetes is increasing in Sweden. However, studies evaluating glycaemic control in children using CSII show inconsistent results. The distribution of responsibility for diabetes self-management between children and parents is often unclear and needs clarification. There is much published support for continued parental involvement and shared diabetes management during adolescence. Guided Self-Determination (GSD) is an empowerment-based, person-centred, reflection and problem solving method intended to guide the patient to become self-sufficient and develop life skills for managing difficulties in diabetes self-management. This method has been adapted for adolescents and parents as Guided Self-Determination-Young (GSD-Y). This study aims to evaluate the effect of an intervention with GSD-Y in groups of adolescents starting on insulin pumps and their parents on diabetes-related family conflicts, perceived health and quality of life (QoL), and metabolic control. Here, we describe the protocol and plans for study enrollment. This study is designed as a randomized, controlled, prospective, multicentre study. Eighty patients between 12-18 years of age who are planning to start CSII will be included. All adolescents and their parents will receive standard insulin pump training. The education intervention will be conducted when CSII is to be started and at four appointments in the first 4 months after starting CSII. The primary outcome is haemoglobin A1c levels. Secondary outcomes are perceived health and QoL, frequency of blood glucose self-monitoring and bolus doses, and usage of carbohydrate counting. The following instruments will be used: Disabkids, 'Check your health', the Diabetes Family Conflict Scale and the Swedish Diabetes Empowerment Scale. Outcomes will be evaluated within and between groups by comparing data at baseline, and at 6 and 12 months after starting treatment. In this

  14. Comparison between a multiple daily insulin injection regimen (basal once-daily glargine plus mealtime lispro) and continuous subcutaneous insulin infusion (lispro) using continuous glucose monitoring in metabolically optimized type 1 diabetes patients: A randomized open-labelled parallel study.

    PubMed

    Ruiz-de-Adana, María Soledad; Dominguez-Lopez, Marta-Elena; Gonzalez-Molero, Inmaculada; Machado, Alberto; Martin, Victor; Cardona, Isabel; de-la-Higuera, Magdalena; Tapia, María-José; Soriguer, Federico; Anarte, María Teresa; Rojo-Martínez, Gemma

    2016-03-18

    Advantages of continuous subcutaneous insulin infusion (CSII) over multiple daily injections with glargine (MDI/G) are still uncertain. We compared CSII vs. MDI/G therapy in unselected patients with type 1 diabetes using continuous glucose monitoring (CGSM). The primary end-points were glycaemic control and quality of life (QOL). A total of 45 patients with long-term diabetes and mean HbA1c values of 8.6±1.8% (70.5±15.4mmol/mol), previously treated with MDI/NPH, were switched to MDI/G for 6 months and then, unfulfilling therapy CSII indication, were randomly assigned to CSII or MDI/G for another six months. We evaluated QOL (EsDqol) and glycaemic control by measuring HbA1c levels, rate of hypoglycaemia, ketoacidosis and CGSM data. After the first phase (MDI/NPH to MDI/G) there was a significant improvement in total EsDQOL (99.72±18.38 vs. 92.07±17.65; p<0.028), a 0.5% decrease in HbA1c values (8.4±1.2 vs. 7.9±0.7% [68±9.7 vs. 63±5.5mmol/mol]; p<0.032), an improvement in glycaemic variability (standard deviation 66.9±14 vs. 59.4±16mg/dl; p<0.05), a decrease in insulin requirements (0.87±0.29 vs. 0.80±0.25U/kg; p<0.049), a decrease in number of severe hypoglycaemia episodes (0.44±0.9 vs. 0.05±0.2; p<0.014), and an increase in periods of normoglycaemia measured with CGSM (15.8±10.9% vs. 23±18.4%; p<0.003). Six months after randomization, significant improvements were seen in the HbA1c (7.9±0.7 vs. 7±0.6% [63±5.5 vs. 53±4.5mmol/mol]; p<0.001) and EsQOL (91.66±22 vs. 84.53±1.63; p<0.045) only in the CSII group. The HbA1c value was significantly lower when compared with the MDI/G group (CSII 7±0.6% [53±4.5mmol/mol] vs. MDI/G 7.6±0.9% [59.6±7.7mmol/mol]; p<0.03). Intensive insulin therapy with CSII vs. MDI/G was associated with better levels of HbA1c in patients with long-term type 1 diabetes. Copyright © 2015 Elsevier España, S.L.U. All rights reserved.

  15. Long-term health economic benefits of sensor-augmented pump therapy vs continuous subcutaneous insulin infusion alone in type 1 diabetes: a U.K. perspective.

    PubMed

    Roze, Stéphane; Smith-Palmer, Jayne; Valentine, William J; Cook, Mark; Jethwa, Manisha; de Portu, Simona; Pickup, John C

    2016-01-01

    Continuous subcutaneous insulin infusion (CSII) is an important treatment option for type 1 diabetes patients unable to achieve adequate glycemic control with multiple daily injections (MDI). Combining CSII with continuous glucose monitoring (CGM) in sensor-augmented pump therapy (SAP) with a low glucose-suspend (LGS) feature may further improve glycemic control and reduce the frequency of hypoglycemia. A cost-effectiveness analysis of SAP + LGS vs. CSII plus self-monitoring of blood glucose (SMBG) was performed to determine the health economic benefits of SAP + LGS in type 1 diabetes patients using CSII in the U.K. Cost-effectiveness analysis was performed using the CORE diabetes model. Treatment effects were sourced from the literature, where SAP + LGS was associated with a projected HbA1c reduction of -1.49% vs. -0.62% for CSII, and a reduced frequency of severe hypoglycemia. The time horizon was that of patient lifetimes; future costs and clinical outcomes were discounted at 3.5% and 1.5% per annum, respectively. Projected outcomes showed that SAP + LGS was associated with higher mean quality-adjusted life expectancy (17.9 vs. 14.9 quality-adjusted life years [QALYs], SAP + LGS vs. CSII), and higher life expectancy (23.8 vs. 21.9 years), but higher mean lifetime direct costs (GBP 125,559 vs. GBP 88,991), leading to an incremental cost-effectiveness ratio (ICER) of GBP 12,233 per QALY gained for SAP + LGS vs. CSII. Findings of the base-case analysis remained robust in sensitivity analyses. For UK-based type 1 diabetes patients with poor glycemic control, the use of SAP + LGS is likely to be cost-effective compared with CSII plus SMBG.

  16. Experiences of continuous subcutaneous insulin infusion in pregnant women with type 1 diabetes during delivery from four Italian centers: a retrospective observational study.

    PubMed

    Fresa, Raffaella; Visalli, Natalia; Di Blasi, Vincenzo; Cavallaro, Vincenzo; Ansaldi, Egle; Trifoglio, Oria; Abbruzzese, Santina; Bongiovanni, Marzia; Agrusta, Mariano; Napoli, Angela

    2013-04-01

    An optimized metabolic control during delivery is mandatory to prevent maternal-neonatal complications. The primary aim of this study was to evaluate the efficacy and safety of continuous subcutaneous insulin infusion (CSII) during delivery in pregnant women with type 1 diabetes. The secondary aim was to assess the impact of real-time continuous glucose monitoring (RT-CGM) added to CSII versus CSII alone. This was a multicenter observational retrospective study. A standardized protocol, to use CSII throughout pregnancy and delivery, foresaw three different insulin basal rates according to blood glucose level: profile A, the last basal rate in use; profile B, preventive 50% reduction of the last basal rate in use; and profile C, 0.1-0.2 U/h for blood glucose level <70 mg/dL, activated just before anesthesia or at the beginning of active labor. An alternative intravenous protocol (IVP) was given in case of complications and relevant metabolic deterioration. Blood glucose in the target range (70-140 mg/dL) throughout delivery and percentage of activation of the IVP were primary outcomes. Sixty-five pregnant women with diabetes included in the study (56-86% cesarean section; 9-14% spontaneous/stimulated vaginal delivery). Mean blood glucose level was 102 ± 31 mg/dL at 0 min, 109 ± 42 mg/dL at 30 min, 120 ± 48 mg/dL at 60 min, and 99 ± 34 mg/dL at 24 h. Mean basal rate during delivery was 0.6 ± 0.4 U/h (profile B). Mean capillary blood glucose (CBG) level was lower in the RT-CGM group relative to the CSII-alone group: 80 ± 14 mg/dL versus 111 ± 32 mg/dL at 0 min (P<0.01), 79 ± 11 mg/dL versus 109 ± 42 mg/dL at 30 min (P<0.02), and 98 ± 20 mg/dL versus 125 ± 51 mg/dL at 60 min (difference not significant). Eleven newborns experienced transient neonatal hypoglycemia. None of the women switched to IVP. No major differences were observed according to delivery procedure. CSII is possible and safe in different types of delivery in selected and educated women. RT

  17. [Continuous insulin therapy versus multiple insulin injections in the management of type 1 diabetes: a longitutinal study].

    PubMed

    Ribeiro, Maria Estela Bellini; Del Roio Liberatore Junior, Raphael; Custodio, Rodrigo; Martinelli Junior, Carlos Eduardo

    2016-01-01

    To compare multiple doses of insulin and continuous insulin infusion therapy as treatment for type 1 diabetes melito. 40 patients with type 1 diabetes melito (21 female) with ages between 10 and 20 years (mean=14.2) and mean duration of diabetes of 7 years used multiple doses of insulin for at least 6 months and after that, continuous insulin infusion therapy for at least 6 months. Each one of the patients has used multiple doses of insulin and continuous insulin infusion therapy. For analysis of HbA1c, mean glycated hemoglobin levels (mHbA1c) were obtained during each treatment period (multiple doses of insulin and continuous insulin infusion therapy period). Although mHbA1c levels were lower during continuous insulin infusion therapy the difference was not statistically significant. During multiple doses of insulin, 14.2% had mHbA1c values below 7.5% vs. 35.71% while on continuous insulin infusion therapy; demonstrating better glycemic control with the use of continuous insulin infusion therapy. During multiple doses of insulin, 15-40 patients have severe hypoglycemic events versus 5-40 continuous insulin infusion therapy. No episodes of ketoacidosis events were recorded. This is the first study with this design comparing multiple doses of insulin and continuous insulin infusion therapy in Brazil showing no significant difference in HbA1c; hypoglycemic events were less frequent during continuous insulin infusion therapy than during multiple doses of insulin and the percentage of patients who achieved a HbA1c less than 7.5% was greater during continuous insulin infusion therapy than multiple doses of insulin therapy. Copyright © 2015 Sociedade de Pediatria de São Paulo. Publicado por Elsevier Editora Ltda. All rights reserved.

  18. Continuous insulin therapy versus multiple insulin injections in the management of type 1 diabetes: a longitutinal study

    PubMed Central

    Ribeiro, Maria Estela Bellini; Liberatore, Raphael Del Roio; Custodio, Rodrigo; Martinelli, Carlos Eduardo

    2016-01-01

    Abstract Objective: To compare multiple doses of insulin and continuous insulin infusion therapy as treatment for type 1 diabetes mellitus. Methods: 40 patients with type 1 diabetes mellitus (21 female) with ages between 10 and 20 years (mean=14.2) and mean duration of diabetes of 7 years used multiple doses of insulin for at least 6 months and after that, continuous insulin infusion therapy for at least 6 months. Each one of the patients has used multiple doses of insulin and continuous insulin infusion therapy. For analysis of HbA1c, mean glycated hemoglobin levels (mHbA1c) were obtained during each treatment period (multiple doses of insulin and continuous insulin infusion therapy period). Results: Although mHbA1c levels were lower during continuous insulin infusion therapy the difference was not statistically significant. During multiple doses of insulin, 14.2% had mHbA1c values below 7.5% vs. 35.71% while on continuous insulin infusion therapy; demonstrating better glycemic control with the use of continuous insulin infusion therapy. During multiple doses of insulin, 15–40 patients have severe hypoglycemic events versus 5–40 continuous insulin infusion therapy. No episodes of ketoacidosis events were recorded. Conclusions: This is the first study with this design comparing multiple doses of insulin and continuous insulin infusion therapy in Brazil showing no significant difference in HbA1c; hypoglycemic events were less frequent during continuous insulin infusion therapy than during multiple doses of insulin and the percentage of patients who achieved a HbA1c less than 7.5% was greater during continuous insulin infusion therapy than multiple doses of insulin therapy. PMID:26826879

  19. Development of a cross-disciplinary continuous insulin infusion protocol for non-critically ill patients in a French university hospital.

    PubMed

    Bernard, Lise; Roche, Béatrice; Batisse, Marie; Maqdasy, Salwan; Terral, Daniel; Sautou, Valérie; Tauveron, Igor

    2016-10-01

    In non-critically ill patients, the use of an insulin syringe pump allows the management of temporary situations during which other therapies cannot be used (failure of subcutaneous injections, awaiting advice from the diabetes team, emergency situations, prolonged corticosteroid therapy, initiation of an artificial nutrition, need for a fasting status, etc.). To manage the risks related to this «never event», the use of a standard validated protocol for insulin administration and monitoring is an essential prerequisite. To this end, a multidisciplinary approach is recommended. With the support of our subcommission «Endocrinology-Diabetology», we proceeded with a «step-by-step process» to create such a standardized protocol: (1) review of all existing protocols in our hospital; (2) overview of the literature data concerning insulin infusion protocols developed by multidisciplinary teams in France and abroad; (3) development of a standardized protocol for non-intensive care unit patients, respecting the current recommendations and adapting it to the working habits of health teams; and (4) validation of the protocol Two protocols based on the same structure but adapted to the health status of the patient have been developed. The protocols are divided in to three parts: (1) golden rules to make the use of the protocol appropriate and safe; (2) the algorithm (a double entry table) corresponding to a dynamic adaptation of insulin doses, clearly defining the target and the 'at risk situations'; and (3) practical aspects of the protocol: preparation of the syringe, treatment initiation and traceability. The protocols have been validated by the institution. Our standardized insulin infusion protocol is simple, easy to implement, safe and is likely to be applicable in diverse care units. However, the efficiency, safety and the workability of our protocols have to be clinically evaluated. © 2016 John Wiley & Sons, Ltd.

  20. An Audit of Clinical Practice in a Single Centre in Kuwait: Management of Children on Continuous Subcutaneous Insulin Infusion and Cardiovascular Risk Factors Screening

    PubMed Central

    Omar, Dina; Alsanae, Hala; Al Khawari, Mona; Abdulrasoul, Majedah; Rahme, Zahraa; Al Refaei, Faisal; Behbehani, Kazem; Shaltout, Azza

    2017-01-01

    Objectives: To audit the current clinical practice of continuous subcutaneous insulin infusion (CSII) for the treatment of type 1 diabetes mellitus (T1D) in children and adolescents attending a single centre in Kuwait. Methods: A one year retrospective audit was performed in children and adolescents with T1D on CSII, who attended the paediatric diabetes clinic, Dasman Diabetes Institute during 2012. The primary outcome measure was glycaemic control as evidenced by glycated haemoglobin (HbA1c) level and the secondary outcome measures were the frequency of monitoring of the risk for microvascular complications and occurrence of acute complications and adverse events. Results: 58 children and adolescents (mean age ± SD: 12.6 ± 4.1 years) were included. Mean HbA1c at baseline was 8.8% (72.7 mmol/mol) and 8.9% (73.8 mmol/mol) at the end of a 12 months observation period. Children with poor control (HbA1c >9.5% (80 mmol/mol) had a significant 1.4% reduction in HbA1c compared with the overall reduction of 0.1% (p=0.7). Rate of screening for cardiovascular risk factors and for long term complications were well documented. However, there was underreporting of acute complications such as severe hypoglycaemia and diabetic ketoacidosis. Only 1.7% of patients discontinued the pump. Conclusion: There was no significant change in HbA1c values at the end of 12 months follow up. However, HbA1c values in poorly controlled children improved. CSII requires care by skilled health professionals as well as education and selection of motivated parents and children. PMID:28400862

  1. A Review of the Security of Insulin Pump Infusion Systems

    PubMed Central

    Paul, Nathanael; Kohno, Tadayoshi; Klonoff, David C

    2011-01-01

    Insulin therapy has enabled patients with diabetes to maintain blood glucose control to lead healthier lives. Today, rather than injecting insulin manually using syringes, a patient can use a device such as an insulin pump to deliver insulin programmatically. This allows for more granular insulin delivery while attaining blood glucose control. Insulin pump system features have increasingly benefited patients, but the complexity of the resulting system has grown in parallel. As a result, security breaches that can negatively affect patient health are now possible. Rather than focus on the security of a single device, we concentrate on protecting the security of the entire system. In this article, we describe the security issues as they pertain to an insulin pump system that includes an embedded system of components, which include the insulin pump, continuous glucose management system, blood glucose monitor, and other associated devices (e.g., a mobile phone or personal computer). We detail not only the growing wireless communication threat in each system component, but also describe additional threats to the system (e.g., availability and integrity). Our goal is to help create a trustworthy infusion pump system that will ultimately strengthen pump safety, and we describe mitigating solutions to address identified security issues. PMID:22226278

  2. A review of the security of insulin pump infusion systems.

    PubMed

    Paul, Nathanael; Kohno, Tadayoshi; Klonoff, David C

    2011-11-01

    Insulin therapy has enabled patients with diabetes to maintain blood glucose control to lead healthier lives. Today, rather than injecting insulin manually using syringes, a patient can use a device such as an insulin pump to deliver insulin programmatically. This allows for more granular insulin delivery while attaining blood glucose control. Insulin pump system features have increasingly benefited patients, but the complexity of the resulting system has grown in parallel. As a result, security breaches that can negatively affect patient health are now possible. Rather than focus on the security of a single device, we concentrate on protecting the security of the entire system. In this article, we describe the security issues as they pertain to an insulin pump system that includes an embedded system of components, which include the insulin pump, continuous glucose management system, blood glucose monitor, and other associated devices (e.g., a mobile phone or personal computer). We detail not only the growing wireless communication threat in each system component, but also describe additional threats to the system (e.g., availability and integrity). Our goal is to help create a trustworthy infusion pump system that will ultimately strengthen pump safety, and we describe mitigating solutions to address identified security issues.

  3. A Review of the Security of Insulin Pump Infusion Systems

    SciTech Connect

    Klonoff, David C.; Paul, Nathanael R; Kohno, Tadayoshi

    2011-01-01

    Insulin therapy has enabled diabetic patients to maintain blood glucose control to lead healthier lives. Today, rather than manually injecting insulin using syringes, a patient can use a device, such as an insulin pump, to programmatically deliver insulin. This allows for more granular insulin delivery while attaining blood glucose control. The insulin pump system features have increasingly benefited patients, but the complexity of the resulting system has grown in parallel. As a result security breaches that can negatively affect patient health are now possible. Rather than focus on the security of a single device, we concentrate on protecting the security of the entire system. In this paper we describe the security issues as they pertain to an insulin pump system that includes an embedded system of components including the insulin pump, continuous glucose management system, blood glucose monitor, and other associated devices (e.g., a mobile phone or personal computer). We detail not only the growing wireless communication threat in each system component, but we also describe additional threats to the system (e.g., availability and integrity). Our goal is to help create a trustworthy infusion pump system that will ultimately strengthen pump safety, and we describe mitigating solutions to address identified security issues both for now and in the future.

  4. Factors associated with improved glycemic control following continuous subcutaneous insulin infusion therapy in patients with type 2 diabetes uncontrolled with bolus-basal insulin regimens: an analysis from the OpT2mise randomized trial.

    PubMed

    Metzger, Muriel; Castañeda, Javier; Reznik, Yves; Giorgino, Francesco; Conget, Ignacio; Aronson, Ronnie; de Portu, Simona; Runzis, Sarah; Lee, Scott W; Cohen, Ohad

    2017-04-04

    This analysis investigated factors associated with the decrease in HbA1c in patients receiving continuous subcutaneous insulin infusion (CSII) in the OpT2mise randomized trial. In this study, patients with type 2 diabetes and HbA1C >8% following multiple daily injections (MDI) optimization were randomized to receive CSII (n = 168) or MDI (n = 163) for 6 months. Patient-related and treatment-related factors associated with decreased HbA1c in the CSII arm were identified by univariate and multivariate analyses. CSII produced a significantly greater reduction in HbA1c than MDI, and the treatment difference increased with baseline HbA1c . In the CSII arm, the only factors significantly associated with decreased HbA1C were higher baseline HbA1C (P<0.001), geographical region (P<0.001), higher educational level (P=0.012), higher total cholesterol level (P=0.002), lower variability of baseline glucose values on continuous glucose monitoring (P<0.001), and the decrease in average fasting self-monitored blood glucose at 6 months (P<0.001). These findings suggest that CSII offers an option to improve glycemic control in a broad range of type 2 diabetes patients in whom control cannot be achieved with MDI. OpT2mise ClinicalTrials.gov number: NCT01182493 (https://clinicaltrials.gov/).

  5. Evaluation of a Novel Continuous Glucose Monitoring-Based Method for Mealtime Insulin Dosing—the iBolus—in Subjects with Type 1 Diabetes Using Continuous Subcutaneous Insulin Infusion Therapy: A Randomized Controlled Trial

    PubMed Central

    Ampudia-Blasco, F. Javier; Laguna, Alejandro; Revert, Ana; Vehì, Josep; Ascaso, Juan F.; Bondia, Jorge

    2012-01-01

    Abstract Objective Prandial insulin dosing is an empirical practice associated frequently with poor reproducibility in postprandial glucose response. Based on continuous glucose monitoring (CGM), a method for prandial insulin administration (iBolus) is presented and evaluated for people with type 1 diabetes using CSII therapy. Subjects and Methods An individual patient's model for a 5-h postprandial period was obtained from 6-day ambulatory CGM and used for iBolus calculation in 12 patients with type 1 diabetes. In a double-blind, crossover study each patient underwent four meal tests with 40 g or 100 g of carbohydrates (CHOs), both on two occasions. For each meal, the iBolus or the traditional bolus (tBolus) was given before mealtime (t0) in a randomized order. We measured the postprandial glycemic response as the area under the curve of plasma glucose (AUC-PG0–5h) and variability as the individual coefficient of variation (CV) of AUC-PG0–5h. The contribution of the insulin-to-CHO ratio, CHO, plasma glucose at t0 (PGt0), and insulin dose to AUC-PG0–5h and its CV was also investigated. Results AUC-PG0–5h was similar with either bolus for 40-g (iBolus vs. tBolus, 585.5±127.5 vs. 689.2±180.7 mg/dL·h) or 100-g (752.1±237.7 vs. 760.0±263.2 mg/dL·h) CHO meals. A multiple regression analysis revealed a significant model only for the tBolus, with PGt0 being the best predictor of AUC-PG0–5h explaining approximately 50% of the glycemic response. Observed variability was greater with the iBolus (CV, 16.7±15.3% vs. 10.1±12.5%) but independent of the factors studied. Conclusions A CGM-based algorithm for calculation of prandial insulin is feasible, although it does not reduce unpredictability of individual glycemic responses. Causes of variability need to be identified and analyzed for further optimization of postprandial glycemic control. PMID:23003329

  6. Neonatal vancomycin continuous infusion: still a confusion?

    PubMed

    Gwee, Amanda; Cranswick, Noel; Metz, David; Coghlan, Benjamin; Daley, Andrew J; Bryant, Penelope A; Curtis, Nigel

    2014-06-01

    Continuous infusions of vancomycin over 24 hours have been shown in adults to reduce drug toxicity, lower treatment costs and require fewer blood samples for therapeutic drug monitoring. They may also improve clinical outcome through earlier attainment of target drug concentrations. In neonates, there is no consensus on vancomycin dosing. We reviewed the literature to assess the evidence for vancomycin dosing regimens for continuous infusion in neonates. Medline and Embase were searched for studies about continuous vancomycin dosing regimens in neonates that reported serum drug concentrations. The search identified 469 articles, of which 5 were relevant. Five prospective studies were included; 2 studies used non-linear mixed effects modeling. Vancomycin was administered with parenteral nutrition or 5% dextrose. Target serum concentrations varied (range: 10-30 mg/L). Four studies used loading doses before continuous infusion; only 1 documented achievement of therapeutic concentrations after the load. The time to a therapeutic concentration was not reported for the other studies. Attainment of target concentrations ranged from 56% to 89% of measurements. Only 1 study compared intermittent to continuous infusions, reporting higher attainment of target concentrations with continuous dosing (82% vs. 46%). No adverse effects were reported, although 3 neonates developed a reversible raised serum creatinine in the setting of septicemia. Continuous infusions of vancomycin in neonates are well tolerated, require less blood sampling and may result in improved attainment of target concentrations. Further prospective studies are needed in this population.

  7. Comparison between sensor-augmented insulin therapy with continuous subcutaneous insulin infusion or multiple daily injections in everyday life: 3-day analysis of glucose patterns and sensor accuracy in children.

    PubMed

    Zucchini, Stefano; Scipione, Mirella; Balsamo, Claudia; Maltoni, Giulio; Rollo, Alessandra; Molinari, Emanuela; Mangoni, Lorenza; Cicognani, Alessandro

    2011-12-01

    Sensor-augmented continuous subcutaneous insulin infusion (CSII) therapy is superior to CSII therapy alone, but little is known on the effectiveness of sensor-augmented multiple daily injections (MDI) therapy. We compared during everyday life mean glucose control and several variability indexes recorded for 3 days by a real-time glucose sensor (Medtronic, Northridge, CA) in two groups of children treated with either CSII or MDI. Fifty-five consecutive subjects were examined: 17 receiving CSII and 38 receiving MDI basal-bolus therapy (age range, 7-22 years). All subjects wore the sensor for 4 days, and 3 days were used for statistical analysis. Mean glucose and SD, coefficient of variation (CV), mean amplitude of glucose excursion (MAGE), mean of daily differences (MODD), continuous overall net glycemic action (CONGA) at 2 and 4 h, blood glucose (BG) rate, area under the curve (AUC) above 180 mg/dL and below 70 mg/dL, Low BG Index (LBGI), and High BG Index (HBGI) were calculated. Patients receiving CSII administered more daily boluses than patients receiving MDI (5.2±1.5 vs. 3.2±0.3, respectively; P=0.001). Mean glucose was lower in the CSII group. AUC above 180 mg/dL and HBGI were higher in the MDI group. CV, CONGA at 2 h, CONGA at 2 h during the day, and HBGI were worse in the MDI group, whereas MODD, LBGI, BG rate, and MAGE were similar. A positive correlation (r=0.95; P<0.05) was found between the paired sensor-meter values. For the glucose values <70 mg/dL, sensitivity was 40%, and specificity was 99%. In our pediatric patients during everyday life sensor-augmented CSII therapy seemed more effective than sensor-augmented MDI therapy, in terms both of glucose mean values and of intraday variability. Mild hypoglycemic episodes and indexes of low BG values were similar in the two groups, although the latter results may be inaccurate because of low sensor sensitivity at low glucose value.

  8. Effects of Liraglutide Combined with Short-Term Continuous Subcutaneous Insulin Infusion on Glycemic Control and Beta Cell Function in Patients with Newly Diagnosed Type 2 Diabetes Mellitus: A Pilot Study.

    PubMed

    Ke, Weijian; Liu, Liehua; Liu, Juan; Chen, Ailing; Deng, Wanping; Zhang, Pengyuan; Cao, Xiaopei; Liao, Zhihong; Xiao, Haipeng; Liu, Jianbin; Li, Yanbing

    2016-01-01

    The objective of this paper is to investigate the effects of liraglutide in combination with short-term continuous subcutaneous insulin infusion (CSII) therapy on glycemic control and beta cell function in patients with newly diagnosed type 2 diabetes mellitus (T2DM). Thirty-nine eligible newly diagnosed T2DM patients were recruited and randomized to receive either of two therapies: short-term CSII alone (CSII alone group) or CSII in combination with liraglutide (CSII + Lira group) for 12 weeks. Blood glucose control, homeostasis model assessment (HOMA) indices, and acute insulin response (AIR) were compared between the two groups. The patients in CSII + Lira group achieved euglycemia with equivalent insulin dosage in shorter time (1 (0) versus 2 (3) days, P = 0.039). HbA1c at the end of study was comparable between two groups (6.3 ± 0.7% versus 6.0 ± 0.5%, for CSII alone group and CSII + Lira group, resp., P = 0.325). The increment of AIR was higher in CSII + Lira group (177.58 (351.57) μU · min/mL versus 58.15 (51.30) μU · min/mL, P < 0.001). However, after stopping liraglutide, its effect on beta cell function disappeared completely. Liraglutide combined with short-term CSII was effective in further improving beta cell function, but the beneficial effects did not sustain after suspension of the therapy.

  9. Numerical and clinical precision of continuous glucose monitoring in Colombian patients treated with insulin infusion pump with automated suspension in hypoglycemia.

    PubMed

    Gómez, Ana M; Marín Sánchez, Alejandro; Muñoz, Oscar M; Colón Peña, Christian Alejandro

    2015-12-01

    Insulin pump therapy associated with continuous glucose monitoring has shown a positive clinical impact on diabetes control and reduction of hypoglycemia episodes. There are descriptions of the performance of this device in other populations, but its precision and accuracy in Colombia and Latin America are unknown, especially in the routine outpatient setting. Data from 33 type 1 and type 2 diabetes patients with sensor-augmented pump therapy with threshold suspend automation, MiniMed Paradigm® Veo™ (Medtronic, Northridge, California), managed at Hospital Universitario San Ignacio (Bogotá, Colombia) and receiving outpatient treatment, were analyzed. Simultaneous data from continuous glucose monitoring and capillary blood glucose were compared, and their precision and accuracy were calculating with different methods, including Clarke error grid. Analyses included 2,262 continuous glucose monitoring -reference paired glucose values. A mean absolute relative difference of 20.1% was found for all measurements, with a value higher than 23% for glucose levels ≤75mg/dL. Global compliance with the ISO criteria was 64.9%. It was higher for values >75mg/dl (68.3%, 1,308 of 1,916 readings), than for those ≤ 75mg/dl (49.4%, 171 of 346 readings). Clinical accuracy, as assessed by the Clarke error grid, showed that 91.77% of data were within the A and B zones (75.6% in hypoglycemia). A good numerical accuracy was found for continuous glucose monitoring in normo and hyperglycemia situations, with low precision in hypoglycemia. The clinical accuracy of the device was adequate, with no significant safety concerns for patients. Copyright © 2015 SEEN. Published by Elsevier España, S.L.U. All rights reserved.

  10. Quality of life in Danish children and adolescents with type 1 diabetes treated with continuous subcutaneous insulin infusion or multiple daily injections.

    PubMed

    Birkebaek, N H; Kristensen, L J; Mose, A H; Thastum, M

    2014-12-01

    The aims of the study were to compare health-related quality of life (HRQoL) in a National Danish population of children and adolescents with type 1 diabetes (T1D) treated with either continuous subcutaneous insulin injection (CSII) or multiple daily insulin injections (MDI), and to investigate whether HRQoL assessments were influenced by treatment duration. Participants were recruited through the Danish Registry for Diabetes in Childhood and Adolescence. A total of 700 children and adolescents (360 girls), 8-17 years, were included. Of these, 295 were treated with CSII (160 for more than one year) and 405 with MDI (238 for more than one year). Participants and their parents completed the Pediatric Quality of Life Inventory Diabetes and Generic Module. HbA1c was analyzed centrally. Parents reported children and adolescents on CSII for more than one year to have less diabetes-related symptoms and worry, less problems in communicating diabetes, and better generic functioning compared with those on MDI. Children and adolescents on CSII for more than one year reported less diabetes-related symptoms, but more treatment problems, and better generic functioning in all subscales except social functioning compared with those on MDI for more than one year. Comparing those on CSII and MDI for less than one year, no differences in HRQoL ratings were found, apart from better rating of treatment barriers in the MDI group. This Danish national study on HRQoL in children and adolescents on CSII or MDI showed better HRQoL in children and adolescents on long time CSII, particularly concerning generic HRQoL. Copyright © 2014 Elsevier Ireland Ltd. All rights reserved.

  11. [Performance of a portable continuous infusion pump (SUREFUSER A) in continuous infusion of 5-FU].

    PubMed

    Kimata, Tsukasa; Sakamoto, Eiji; Kawachi, Aya; Takahashi, Yayoi; Kuroki, Asako; Nakamura, Masashi; Kawade, Yoshihiro; Tokui, Kenji; Suzuki, Tatsuya; Oyama, Takashi; Uchida, Toshiki; Yamada, Tomonori; Kondoh, Masahiro; Ogura, Michinori

    2010-08-01

    Therapy with mFOLFOX6/FOLFIRI used in treating colorectal cancer is typical of the regimens performed in outpatient settings. In this therapy, 46-h continuous infusion of 5-fluorouracil (5-FU) with concomitant oxaliplatin and irinotecan hydrochloride is conducted. The portable continuous infusion pump that makes continuous infusion possible has a non-electric structure, so variation in the infusion rate is seen. There are known effects of 5-FU concentration and temperature, and many studies have reported on the precision. In our hospital, we have experienced many cases of incomplete infusion and delays for the above reasons. We changed the specifications of the infusion pump to correspond to the kinematic viscosity of 5-FU and made all drug solution amounts uniform. We measured the time required to administer the drug solution from the time the infusion was started (recorded by a nurse) and the time it was completed (recorded by the patient), and confirmed the precision of the pump after the changes were made. It was found that while there was a decrease in the infusion rate at which the effect of the kinematic viscosity of 5-FU is seen, the mean infusion time was kept to within 46+/-10% hours in more than 90% of patients. There were no effects from concentration differences in 5-FU, and the completion time was reduced. The management and lifestyles of individual patients are potential factors in precision errors, and it is important to explain in advance to patients the necessity of secure fixation and infusion pump problems that might occur.

  12. Continuous Subcutaneous Insulin Infusion in Neonates and Infants Below 1 Year: Analysis of Initial Bolus and Basal Rate Based on the Experiences from the German Working Group for Pediatric Pump Treatment.

    PubMed

    Kapellen, Thomas M; Heidtmann, Bettina; Lilienthal, Eggert; Rami-Merhar, Birgit; Engler-Schmidt, Charlotte; Holl, Reinhard W

    2015-12-01

    Diabetes mellitus is rare in young infants and neonates. Continuous subcutaneous insulin infusion (CSII) is used most frequently for insulin treatment in this age group. However, the individual doctor's experience is scarce because of the low prevalence of diabetes in this age. For this study patients treated with CSII with an age below 1 year were selected from the German/Austrian DPV (Diabetes-Patienten-Verlaufsdokumentation) database, and basal rate and bolus calculation were described. For all patients less than 1 year of age, basal rate and mealtime boluses were compared among infants with type 1 diabetes mellitus (T1DM), infants with neonatal diabetes mellitus (NDM), and infants with antibody status unknown diabetes mellitus (AUDM). Fifty-eight patients with T1DM, 67 neonates with NDM, and 43 infants with early diabetes development after 6 months and negative β-cell antibodies (AUDM) could be analyzed. T1DM patients at onset required a median total insulin amount of 0.83 IU/kg of body weight, whereas NDM patients required 0.74 IU/kg of body weight (P = 0.63). Basal insulin requirement however, was different between the two groups (0.56 IU/kg of body weight in NDM vs. 0.43 IU/kg in T1DM) (P = 0.036). The percentage basal profile of NDM and T1DM patients was quite similar to children at the age of 1-5 years. The proportion of prandial insulin at onset was significantly different (32% in NDM vs. 53% in T1DM) (P < 0.00001). AUDM patients showed almost similar data to T1DM patients. The pattern of mealtime bolus insulin was not different among the groups. The presented data can be used as an initial guide value to start CSII treatment in neonates and infants. To be on the safe side we recommend the lower quartile for the dosage as the starting value in nonketotic patients.

  13. Glucose-insulin and potassium infusions in septic shock.

    PubMed

    Hamdulay, Shahir S; Al-Khafaji, Ali; Montgomery, Hugh

    2006-03-01

    Glucose-insulin and potassium (GIK) infusions are beneficial in treating ischemic myocardial depression. Myocardial depression is also an important feature in septic shock. We describe two cases of pressor-resistant hypodynamic septic shock that responded to high-dose GIK infusions. In each case, hemodynamic profiles improved sufficiently to allow withdrawal of vasopressor agents. Further assessment of GIK in patients with hypodynamic septic shock is necessary to confirm efficacy and prognostic significance.

  14. Insulin-mediated glucose disposal in type 1 (insulin-dependent) diabetic subjects treated by continuous subcutaneous or intraperitoneal insulin fusion.

    PubMed

    Beylot, M; Khalfallah, Y; Laville, M; Sautot, G; Dechaud, H; Serusclat, P; Berthezene, F; Riou, J P; Mornex, R

    1987-01-01

    In order to determine if intraperitoneal insulin infusion could improve the insulin resistance of type 1 diabetic patients we have used the englycaemic insulin clamp technique in order to study the effects of insulin on glucose disposal in four C peptide negative type 1 diabetic patients treated by continuous subcutaneous or intraperitoneal insulin infusion and in five control subjects. Compared to control subjects, the diabetic patients treated by subcutaneous insulin infusion had a decreased maximal capacity of glucose utilization (diabetics: 12.6 +/- 0.3 mg.kg-1.min-1; controls: 15.7 +/- 0.7 mg/kg-1.min-1, p less than 0.01) and a trend towards higher half-maximally effective insulin concentrations (diabetics: 70 +/- 11 mU/l-1, controls: 48 +/- 4 mU/l-1). Treatment of the diabetic patients by intraperitoneal insulin infusion for 2 months decreased their mean peripheral free insulin levels (during subcutaneous infusion: 23.5 +/- 2.2 mU/l-1; during intraperitoneal infusion: 18.4 +/- 1.4 mU/l-1, p less than 0.05). However, mean daily insulin requirements were not decreased (during subcutaneous infusion: 0.59 +/- 0.05 U/kg-1.day-1; during intraperitoneal infusion: 0.57 +/- 0.03 U/kg-1.min-1). Moreover, the diabetic patients had a consistently lower maximal capacity of glucose utilization (12.6 +/- 0.7 mg kg-1.min-1) than control subjects (p less than 0.01) without modification of the half-maximally effective insulin concentration (62 +/- 10 mU.l-1). In conclusion, the only benefit of intraperitoneal insulin infusion was a reduction of peripheral free insulin levels; this decrease of peripheral insulinaemia was not associated with an improvement in the insulin resistance of diabetic patients.

  15. Induction of hyperlipidemia by intravenous infusion of tallow emulsion causes insulin resistance in Holstein cows.

    PubMed

    Pires, J A A; Souza, A H; Grummer, R R

    2007-06-01

    The objective was to test whether the induction of elevated blood nonesterified fatty acids (NEFA) by i.v. infusion of a tallow emulsion altered glucose tolerance and responsiveness to insulin in Holstein cows. Six non-lactating, nongestating Holstein cows were assigned to a crossover design. One cow was excluded before initiation of the experiment because of complications from mastitis. Treatments consisted of 11-h i.v. infusions of saline (control) or a 20% (wt/vol) triacylglycerol (TG) emulsion derived from tallow (tallow) to elevate plasma NEFA. Each period consisted of two 11-h infusions (INF1 and INF2), separated by 1 d in which cows were not infused. Intravenous glucose tolerance tests (IVGTT) and insulin challenges (IC) were performed 8 h after initiation of INF1 and INF2, respectively. The infusion of treatments continued during the 3 h of sampling for IVGTT and IC. Cows were fed every 4 h at a rate to meet energy requirements for 5 d prior to each period, and every 2 h during the first 8 h of infusions. Infusion of tallow induced hyperlipidemia by increasing plasma NEFA (295 +/- 9 vs. 79 +/- 7 microEq/L), serum TG (41.0 +/- 6 vs. 11.4 +/- 4.4 mg/dL), and glycerol (0.81 +/- 0.09 vs. 0.23 +/- 0.1 mg/dL) concentrations during INF1. During INF2, tallow treatment increased plasma NEFA (347 vs. 139 +/- 18 microEq/L), serum TG (20.8 +/- 4.6 vs. 13.1 +/- 2.3 mg/dL), and glycerol (0.88 +/- 0.04 vs. 0.31 +/- 0.02 mg/dL) concentrations. Induction of hyperlipidemia impaired glucose clearance during IVGTT, despite the greater endogenous insulin response to the glucose infusion, leading to a lower insulin sensitivity index [0.29 vs. 1.88 +/- 0.31 x 10(-4) min(-1)/(microIU/mL)]. Accordingly, hyperlipidemia impaired glucose clearance during IC (1.58 vs. 2.72 %/min), reflecting lower responsiveness to insulin. These data show that induction of hyperlipidemia causes insulin resistance in Holstein cows by impairing both sensitivity and maximum responsiveness to insulin. The

  16. Early Detection of Infusion Set Failure During Insulin Pump Therapy in Type 1 Diabetes.

    PubMed

    Cescon, Marzia; DeSalvo, Daniel J; Ly, Trang T; Maahs, David M; Messer, Laurel H; Buckingham, Bruce A; Doyle, Francis J; Dassau, Eyal

    2016-11-01

    Insulin infusion set failure resulting in prolonged hyperglycemia or diabetic ketoacidosis can occur with pump therapy in type 1 diabetes. Set failures are frequently characterized by variable and unpredictable patterns of increasing glucose values despite increased insulin infusion. Early detection may minimize the risk of prolonged hyperglycemia, an important consideration for automated insulin delivery and closed-loop applications. A novel algorithm designed to alert the patient to the onset of infusion set failure was developed based upon continuous glucose sensor values and insulin delivered from an insulin pump. The method was calibrated on 12 weeks of infusion set wear without failures recorded by 4 patients in ambulatory conditions and prospectively validated on 18 weeks of infusion set wear with and without failures belonging to 9 other subjects in ambulatory conditions. The algorithm, evaluated retrospectively, identified a failure 2.52 ± 1.91 days ahead of the actual event as recorded by the clinical team, corresponding to 50% sensitivity, 66% specificity and 55% accuracy. If set failure alarms had been activated in real time, the average time >180 mg/dl would be reduced from 82.7 ± 40.9 hours/week/subject (without alarm) to 58.8 ± 31.1 hours/week/subject (with alarm), corresponding to a potential 29% reduction in time spent >180mg/dl. The proposed method for early detection of infusion set failure based on glucose sensor and insulin data demonstrated favorable results on retrospective data and may be implemented as an additional safeguard in a future fully automated closed-loop system. © 2016 Diabetes Technology Society.

  17. A Hazard Analysis for a Generic Insulin Infusion Pump

    PubMed Central

    Zhang, Yi; Jones, Paul L.; Jetley, Raoul

    2010-01-01

    Background Researchers at the Food and Drug Administration (FDA)/Center for Device and Radiological Health/Office of Science and Engineering Laboratories have been exploring the concept of model-based engineering as a means for improving the quality of medical device software. Insulin pumps were chosen as a research subject because their design provides the desired degree of research complexity and these types of devices present an ongoing regulatory challenge. Methods Insulin pump hazards and their contributing factors are considered in the context of a highly abstract generic insulin infusion pump (GIIP) model. Hazards were identified by consulting with manufacturers, pump users, and clinicians; by reviewing national and international standards and adverse event reports collected by the FDA; and from workshops sponsored by Diabetes Technology Society. This information has been consolidated in tabular form to facilitate further community analysis and discussion. Results A generic insulin infusion pump model architecture has been established. A fairly comprehensive hazard analysis document, corresponding to the GIIP model, is presented in this article. Conclusions We believe that this work represents the genesis of an insulin pump safety reference standard upon which future insulin pump designs can be based to help ensure a basic level of safety. More interaction with the diabetes community is needed to assure the quality of this safety modeling process. PMID:20307387

  18. Determining starting basal rates of insulin infusion for insulin pump users: a comparison between methods

    PubMed Central

    Chow, Nelson; Shearer, Daniel; Tildesley, Hamish G; Aydin Plaa, Jessica; Pottinger, Betty; Pawlowska, Monika; White, Adam; Priestman, Anne; Ross, Stuart A; Tildesley, Hugh D

    2016-01-01

    Objective We aimed to assess the accuracy and safety of presently available methods of estimating starting basal insulin rates for patients with type 1 and 2 diabetes, and to compare them against an empirically derived standard basal rate and a newly developed regression formula. Research design and methods Data on 61 patients with type 1 diabetes on continuous subcutaneous insulin infusion (CSII) therapy and 34 patients with type 2 diabetes on CSII were reviewed. Patient data were first analyzed for correlations between initial patient parameters and final basal rates. Starting basal rates were then retrospectively calculated for these patients according to the weight-based method (WB-M), the total daily dose (TDD) of insulin method (TDD-M), a flat empiric value, and a new formula developed by regression analysis of clinical data. These 4 methods were subsequently compared in their accuracy and potential risk of hypoglycemia. Results For type 1 diabetes, patient weight and TDD of long-acting insulin correlated with final basal rates. Both the regression formula and the TDD-M appeared safer than the WB-M and empirical estimates. For type 2 diabetes, only patient TDD of long-acting insulin correlated with final basal rates. The regression formula was significantly more accurate for patients with type 2 diabetes overall, but the TDD-M estimate was marginally safer. Conclusions The pre-existing TDD-M was found to be the safest presently recommended estimate of initial basal rates for pump initiation in both type 1 and 2 diabetes. The best-fit regression was found to have potential use for type 2 CSII initiation. PMID:26977305

  19. Intraperitoneal insulin infusion: treatment option for type 1 diabetes resulting in beneficial endocrine effects beyond glycaemia.

    PubMed

    van Dijk, P R; Logtenberg, S J J; Gans, R O B; Bilo, H J G; Kleefstra, N

    2014-10-01

    Continuous intraperitoneal insulin infusion (CIPII) is a treatment option for patients with type 1 diabetes mellitus who fail to reach adequate glycaemic control despite intensive subcutaneous (SC) insulin therapy. CIPII has clear advantages over SC insulin administration in terms of pharmacokinetic and pharmacodynamic properties and has been shown to improve glycaemic regulation. Due to the delivery of insulin predominantly in the portal vein, as opposed to systemically, CIPII offers a unique research model to investigate the effects of insulin on endocrine and metabolic parameters in vivo. The aim of the present article is to provide an overview of the literature with respect to the effects of CIPII on glucose management, quality of life, complications and costs, with additional focus on metabolic and endocrine aspects. Finally, future use and research objectives are discussed.

  20. Stimulation of muscle protein synthesis by long-term insulin infusion in severely burned patients.

    PubMed Central

    Sakurai, Y; Aarsland, A; Herndon, D N; Chinkes, D L; Pierre, E; Nguyen, T T; Patterson, B W; Wolfe, R R

    1995-01-01

    OBJECTIVE: To determine if long-term (7 days) infusion of insulin can ameliorate altered protein kinetics in skeletal muscle of severely burned patients and to investigate the hypothesis that changes in protein kinetics during insulin infusion are associated with an increased rate of transmembrane amino acid transport from plasma into the intracellular free amino acid pool. SUMMARY BACKGROUND DATA: In critically ill patients, vigorous nutritional support alone may often fail to entirely curtail muscle catabolism; insulin stimulates muscle protein synthesis in normal volunteers. METHODS: Nine patients with severe burns were studied once during enteral feeding alone (control period), and once after 7 days of high-dose insulin. The order of treatment with insulin was randomized. Data were derived from a model based on a primed-continuous infusion of L-[15N]phenylalanine, sampling of blood from the femoral artery and vein, and biopsies of the vastus lateralis muscle. RESULTS: Net leg muscle protein balance was significantly (p < 0.05) negative during the control period. Exogenous insulin eliminated this negative balance by stimulating protein synthesis approximately 350% (p < 0.01). This was made possible in part by a sixfold increase in the inward transport of amino acids from blood (p < 0.01). There was also a significant increase in leg muscle protein breakdown. The new rates of synthesis, breakdown, and inward transport during insulin were in balance, such that there was no difference in the intracellular phenylalanine concentration from the control period. The fractional synthetic rate of protein in the wound was also stimulated by insulin by approximately 50%, but the response was variable and did not reach significance. CONCLUSIONS: Exogenous insulin may be useful in promoting muscle protein synthesis in severely catabolic patients. PMID:7677459

  1. Continuous postoperative insulin infusion reduces deep sternal wound infection in patients with diabetes undergoing coronary artery bypass grafting using bilateral internal mammary artery grafts: a propensity-matched analysis.

    PubMed

    Ogawa, Shinji; Okawa, Yasuhide; Sawada, Koshi; Goto, Yoshihiro; Yamamoto, Masanori; Koyama, Yutaka; Baba, Hiroshi; Suzuki, Takahiko

    2016-02-01

    Deep sternal wound infection (DSWI), especially in patients with diabetes mellitus (DM), is a major concern after coronary artery bypass grafting (CABG) with bilateral internal mammary artery (BIMA) grafts. We evaluated the risk of DSWI and other clinical outcomes between continuous insulin infusion therapy (CIT) and insulin sliding scale therapy (IST) in a cohort of DM patients who underwent CABG with BIMA. The clinical records of DM patients who underwent isolated CABG with BIMA were retrospectively reviewed. The study population consisted of 95 patients who received CIT and 126 patients who received IST. Furthermore, a one-to-one matched analysis based on estimated propensity scores for patients who received CIT or IST yielded two groups comprising 58 patients each. The proportion of patients with DSWI, overall survival rates and major adverse cardiac events were compared between the two groups in the overall and the propensity-matching cohort. The prevalence of DSWI requiring debridement and closure was significantly reduced in the CIT group compared with that in the IST group [1/95 (1.1%) vs 9/126 (7.1%), P = 0.031]; these results were not attenuated even after propensity-matching analysis [0/58 (0%) vs 6/58 (10.3%), P = 0.031]. The mean preoperative glucose levels were similar between the two groups (157.5 ± 54.6 vs 176.1 ± ±70 mg/dl, P = 0.063), whereas the mean glucose values were significantly lower on the first and second operative days in the CIT group than in the IST group (132.9 ± 44.1 vs 197.8 ± 78.6 mg/dl, P < 0.0001; 153.5 ± 58.8 vs 199.6 ± 89.1 mg/dl, P < 0.0001, respectively). The glucose variability levels within 24 h postoperatively were significantly higher in the IST group (46.1 ± 19.4 vs 66.4 ± 26.8 mg/dl, P < 0.0001). The 30-day and 1-year survival rates were similar between the two groups (100 vs 99.2%, P = 0.384; 96.6 vs 94.4%, P = 0.454). No results were changed in the propensity-matching models. The CIT approach reduced the

  2. The direct cost of intravenous insulin infusions to the NHS in England and Wales.

    PubMed

    Rajendran, Rajesh; Scott, Anne; Rayman, Gerry

    2015-08-01

    The cost of intravenous insulin infusion to the NHS is unknown. The aim of this study was to estimate the direct cost of insulin infusions to the NHS in England and Wales in the first 24-hour period of infusion. Data from the National Inpatient Diabetes Audit 2013 in the UK were used to estimate the number of insulin infusions in use across England and Wales. Costs were calculated for six models for setting up and maintenance of insulin infusions, depending on the extent of involvement of different healthcare professionals in the UK. In this study, the direct costs of intravenous insulin infusions to the NHS in England and Wales have been estimated to vary from £6.4-8.5 million in the first 24-hour period on infusion. More appropriate use of these infusions could result in substantial cost savings.

  3. Analysis of the environmental impact of insulin infusion sets based on loss of resources with waste.

    PubMed

    Pfützner, Andreas; Musholt, Petra B; Malmgren-Hansen, Bjoern; Nilsson, Nils H; Forst, Thomas

    2011-07-01

    Insulin pump therapy [continuous subcutaneous insulin infusion (CSII)] requires regular change of infusion sets every 2-3 days in order to minimize the risk of skin irritations or other adverse events. This has been discussed to be a potential burden to the environment. The purpose of this analysis was to perform an environmental assessment of insulin pump infusion sets based on loss of resources occurring during incineration of the discarded products and by means of a lifecycle concept used to weight a material in relation to its rareness on earth and its consumption. In addition to five infusion sets (Inset30, InsetII, Comfort, Quick-set, and Cleo), a patch pump (Omnipod) was also included in this analysis. The annual loss in waste of the so called "person reserve" of 3 days of catheter use was compared with daily consumption of a cup of coffee in a disposable paper cup and to a soft drink in an aluminum can. The weight-based loss in resources through waste for the infusion sets (except for Cleo) corresponded to 70-200% of the loss of resources for a coffee cup (Cleo, 320%; Omnipod, 1,821,600%) and to 1-3% of the loss from an aluminum soft drink can (Cleo, 5%; Omnipod, 31,200%). The loss or resources by use of infusion sets used in insulin pump therapy appears to be low and is similar to the burden induced by the uptake of one cup of coffee per day. The loss or resources with regular CSII is considerably lower than the loss or resources induced by patch pumps. © 2011 Diabetes Technology Society.

  4. Effects of glucosamine infusion on insulin secretion and insulin action in humans.

    PubMed

    Monauni, T; Zenti, M G; Cretti, A; Daniels, M C; Targher, G; Caruso, B; Caputo, M; McClain, D; Del Prato, S; Giaccari, A; Muggeo, M; Bonora, E; Bonadonna, R C

    2000-06-01

    Glucose toxicity (i.e., glucose-induced reduction in insulin secretion and action) may be mediated by an increased flux through the hexosamine-phosphate pathway. Glucosamine (GlcN) is widely used to accelerate the hexosamine pathway flux, independently of glucose. We tested the hypothesis that GlcN can affect insulin secretion and/or action in humans. In 10 healthy subjects, we sequentially performed an intravenous glucose (plus [2-3H]glucose) tolerance test (IVGTT) and a euglycemic insulin clamp during either a saline infusion or a low (1.6 micromol x min(-1) x kg(-1)) or high (5 micromol x min(-1) x kg(-1) [n = 5]) GlcN infusion. Beta-cell secretion, insulin (SI*-IVGTT), and glucose (SG*) action on glucose utilization during the IVGTT were measured according to minimal models of insulin secretion and action. Infusion of GlcN did not affect readily releasable insulin levels, glucose-stimulated insulin secretion (GSIS), or the time constant of secretion, but it increased both the glucose threshold of GSIS (delta approximately 0.5-0.8 mmol/l, P < 0.03-0.01) and plasma fasting glucose levels (delta approximately 0.3-0.5 mmol/l, P < 0.05-0.02). GlcN did not change glucose utilization or intracellular metabolism (glucose oxidation and glucose storage were measured by indirect calorimetry) during the clamp. However, high levels of GlcN caused a decrease in SI*-IVGTT (delta approximately 30%, P < 0.02) and in SG* (delta approximately 40%, P < 0.05). Thus, in humans, acute GlcN infusion recapitulates some metabolic features of human diabetes. It remains to be determined whether acceleration of the hexosamine pathway can cause insulin resistance at euglycemia in humans.

  5. Cognitively impaired elderly exhibit insulin resistance and no memory improvement with infused insulin.

    PubMed

    Morris, Jill K; Vidoni, Eric D; Mahnken, Jonathan D; Montgomery, Robert N; Johnson, David K; Thyfault, John P; Burns, Jeffrey M

    2016-03-01

    Insulin resistance is a risk factor for Alzheimer's disease (AD), although its role in AD etiology is unclear. We assessed insulin resistance using fasting and insulin-stimulated measures in 51 elderly subjects with no dementia (ND; n = 37) and with cognitive impairment (CI; n = 14). CI subjects exhibited either mild CI or AD. Fasting insulin resistance was measured using the homeostatic model assessment of insulin resistance (HOMA-IR). Insulin-stimulated glucose disposal was assessed using the hyperinsulinemic-euglycemic clamp to calculate glucose disposal rate into lean mass, the primary site of insulin-stimulated glucose disposal. Because insulin crosses the blood-brain barrier, we also assessed whether insulin infusion would improve verbal episodic memory compared to baseline. Different but equivalent versions of cognitive tests were administered in counterbalanced order in the basal and insulin-stimulated state. Groups did not differ in age or body mass index. Cognitively impaired subjects exhibited greater insulin resistance as measured at fasting (HOMA-IR; ND: 1.09 [1.1] vs. CI: 2.01 [2.3], p = 0.028) and during the hyperinsulinemic clamp (glucose disposal rate into lean mass; ND: 9.9 (4.5) vs. AD 7.2 (3.2), p = 0.040). Cognitively impaired subjects also exhibited higher fasting insulin compared to ND subjects, (CI: 8.7 [7.8] vs. ND: 4.2 [3.8] μU/mL; p = 0.023) and higher fasting amylin (CI: 24.1 [39.1] vs. 8.37 [14.2]; p = 0.050) with no difference in fasting glucose. Insulin infusion elicited a detrimental effect on one test of verbal episodic memory (Free and Cued Selective Reminding Test) in both groups (p < 0.0001) and no change in performance on an additional task (delayed logical memory). In this study, although insulin resistance was observed in cognitively impaired subjects compared to ND controls, insulin infusion did not improve memory. Furthermore, a significant correlation between HOMA-IR and glucose disposal rate was present only in ND

  6. Proportional Insulin Infusion in Closed-Loop Control of Blood Glucose

    PubMed Central

    Grasman, Johan

    2017-01-01

    A differential equation model is formulated that describes the dynamics of glucose concentration in blood circulation. The model accounts for the intake of food, expenditure of calories and the control of glucose levels by insulin and glucagon. These and other hormones affect the blood glucose level in various ways. In this study only main effects are taken into consideration. Moreover, by making a quasi-steady state approximation the model is reduced to a single nonlinear differential equation of which parameters are fit to data from healthy subjects. Feedback provided by insulin plays a key role in the control of the blood glucose level. Reduced β-cell function and insulin resistance may hamper this process. With the present model it is shown how by closed-loop control these defects, in an organic way, can be compensated with continuous infusion of exogenous insulin. PMID:28060898

  7. Clinical applications of continuous infusion chemotherapy ahd concomitant radiation therapy

    SciTech Connect

    Rosenthal, C.J.; Rotman, M.

    1986-01-01

    This book presents information on the following topics: theoretical basis and clinical applications of 5-FU as a radiosensitizer; treatment of hepatic metastases from gastro intestingal primaries with split course radiation therapy; combined modality therapy with 5-FU, Mitomycin-C and radiation therapy for sqamous cell cancers; treatment of bladder carcinoma with concomitant infusion chemotherapy and irradiation; a treatment of invasiv bladder cancer by the XRT/5FU protocol; concomitant radiation therapy and doxorubicin by continuous infusion in advanced malignancies; cis platin by continuous infusion with concurrent radiation therapy in malignant tumors; combination of radiation with concomitant continuous adriamycin infusion in a patient with partially excised pleomorphic soft tissue sarcoma of the lower extremeity; treatment of recurrent carcinoma of the paranasal sinuses using concomitant infusion cis-platinum and radiation therapy; hepatic artery infusion for hepatic metastases in combination with hepatic resection and hepatic radiation; study of simultaneous radiation therapy, continuous infusion, 5FU and bolus mitomycin-C; cancer of the esophagus; continuous infusion VP-16, bolus cis-platinum and simultaneous radiation therapy as salvage therapy in small cell bronchogenic carcinoma; and concomitant radiation, mitomycin-C and 5-FU infusion in gastro intestinal cancer.

  8. Prolonged glucose infusion into conscious rats inhibits early steps in insulin signalling and induces translocation of GLUT4 and protein kinase C in skeletal muscle.

    PubMed

    Houdali, B; Nguyen, V; Ammon, H P T; Haap, M; Schechinger, W; Machicao, F; Rett, K; Häring, H-U; Schleicher, E D

    2002-03-01

    Previous studies on diabetic patients have shown that hyperglycaemia increases glucose uptake in an apparently insulin-independent manner. However, the molecular mechanism has not been clarified. We studied rats receiving continuous glucose infusion to address this question. In this animal model, rats accommodate systemic glucose oversupply and rapidly develop insulin resistance. Glucose infusion increased both plasma glucose and insulin concentrations to peak after one day. In spite of continuous glucose infusion normoglycaemia was reached after 5 days while insulin concentrations remained higher. Focusing our studies in day 2 (hyperglycaemia/hyperinsulinaemia) and day 5 (normoglycaemia/hyperinsulinaemia) we found, particularly in day 5, that the early steps of the insulin signalling cascade in skeletal muscle of glucose-infused rats were not more activated when compared to control animals as assessed by a comparable phosphorylation of the insulin receptor, IRS-1 and PKB and by an unaltered IRS-1-associated Ptd(Ins) 3' kinase activity. Continuous glucose infusion induced GLUT4 protein expression and translocation to the plasma membrane while neither expression nor translocation of GLUT1 was affected. Translocation of PKC- betaI, - betaII (> threefold) and -alpha, -theta (to a lesser extent) to the plasma membrane was significantly induced after 2 days but not after 5 days of glucose infusion when normoglycaemia was reached. Our data support the hypothesis that continuous glucose infusion induces translocation of GLUT4 while the early steps of the insulin signalling cascade were not increased. These effects could be mediated by activation of PKC.

  9. The relationship between the frequency of self-monitoring of blood glucose and glycemic control in patients with type 1 diabetes mellitus on continuous subcutaneous insulin infusion or on multiple daily injections

    PubMed Central

    Murata, Takashi; Tsuzaki, Kokoro; Yoshioka, Fumi; Okada, Hiroshi; Kishi, Junichiro; Yamada, Kazunori; Sakane, Naoki

    2015-01-01

    Aims/Introduction We investigated the relationship between the frequency of self-monitoring of blood glucose (SMBG) and glycemic control in type 1 diabetes mellitus patients on continuous subcutaneous insulin infusion (CSII) or on multiple daily injections (MDI) using data management software. Materials and Methods We recruited 148 adult type 1 diabetes mellitus patients (CSII n = 42, MDI n = 106) and downloaded their SMBG records to the MEQNET™ SMBG Viewer software (Arkray Inc., Kyoto, Japan). The association between the SMBG frequency and the patients' hemoglobin A1c (HbA1c) levels was analyzed using the χ2-test and linear regression analysis was carried out to clarify their relationship. Results The odds ratio of achieving a target HbA1c level of <8% (63.9 mmol/mol) was significantly higher in subjects with SMBG frequencies of ≥3.5 times/day compared with those with SMBG frequencies of <3.5 times/day in the CSII group (odds ratio 7.00, 95% confidence interval 1.72–28.54), but not in the MDI group (odds ratio 1.35, 95% CI 0.62–2.93). A significant correlation between SMBG frequency and the HbA1c level was detected in the CSII group (HbA1c [%] = –0.24 × SMBG frequency [times/day] + 8.60 [HbA1c {mmol/L} = –2.61 × SMBG frequency {times/day} + 70.5], [r = –0.384, P = 0.012]), but not in the MDI group. Conclusions A SMBG frequency of <3.5 times per day appeared to be a risk factor for poor glycemic control (HbA1c ≥8%) in type 1 diabetes mellitus patients on CSII. PMID:26543543

  10. Insulin independence following isolated islet transplantation and single islet infusions.

    PubMed

    Markmann, James F; Deng, Shaoping; Huang, Xiaolun; Desai, Niraj M; Velidedeoglu, Ergun H; Lui, Chengyang; Frank, Adam; Markmann, Eileen; Palanjian, Maral; Brayman, Kenneth; Wolf, Bryan; Bell, Ewan; Vitamaniuk, Marko; Doliba, Nicolai; Matschinsky, Franz; Barker, Clyde F; Naji, Ali

    2003-06-01

    To restore islet function in patients whose labile diabetes subjected them to frequent dangerous episodes of hypoglycemic unawareness, and to determine whether multiple transplants are always required to achieve insulin independence. The recent report by the Edmonton group documenting restoration of insulin independence by islet transplantation in seven consecutive patients with type 1 diabetes differed from previous worldwide experience of only sporadic success. In the Edmonton patients, the transplanted islet mass critical for success was approximately more than 9,000 IEq/kg of recipient body weight and required two or three separate transplants of islets isolated from two to four cadaveric donors. Whether the success of the Edmonton group can be recapitulated by others, and whether repeated transplants using multiple donors will be a universal requirement for success have not been reported. The authors report their treatment with islet transplantation of nine patients whose labile type 1 diabetes was characterized by frequent episodes of dangerous hypoglycemia. In each of the seven patients who have completed the treatment protocol (i.e., one or if necessary a second islet transplant), insulin independence has been achieved. In five of the seven patients only a single infusion of islets was required. To date, only one recipient has subsequently lost graft function, after an initially successful transplant. This patient suffered recurrent hyperglycemia 9 months after the transplant. This report confirms the efficacy of the Edmonton immunosuppressive regimen and indicates that insulin independence can often be achieved by a single transplant of sufficient islet mass.

  11. Insulin Infusion Set Use: European Perspectives and Recommendations

    PubMed Central

    Adolfsson, Peter; Alkemade-van Zomeren, Marije; Bolli, Geremia B.; Charpentier, Guillaume; Cobelli, Claudio; Danne, Thomas; Girelli, Angela; Mueller, Heiko; Verderese, Carol A.; Renard, Eric

    2016-01-01

    Abstract Insulin pump users worldwide depend on insulin infusion sets (IISs) for predictable delivery of insulin to the subcutaneous tissue. Yet emerging data indicates that IISs are associated with many pump-related adverse events and may contribute to potentially life-threatening problem of unexplained hyperglycemia. The relative scarcity of published research on IISs to date, the heterogeneity of regional IIS practices, and the increasing demand for international standards guiding their use prompted convening of a panel of diabetologists and diabetes nurse educators last February, in Milan, Italy, to discuss a framework for optimizing IIS practice in Europe. The multinational panel was tasked, first, with identifying the often-overlooked IIS issues that can affect patients' experience of pump therapy—e.g., partial or complete blockage of the cannula, skin pathologies, unpredictable variations in insulin absorption, dislodgment, and the demands of site rotation and set changes—and, second, with establishing direction for developing cohesive protocols to assure long-term success. As reported in this article, the panel examined IIS-related complications of pump therapy encountered in clinical practice, considered country-wide policies to prevent and mitigate such complications, and updated priorities for improving IIS education on issues of device selection, skin care, and troubleshooting unexplained hyperglycemia. These recommendations may be more relevant with the possibility of closed-loop systems available in the near future. PMID:27526329

  12. Is continuous infusion of imipenem always the best choice?

    PubMed

    Suchánková, Hana; Lipš, Michal; Urbánek, Karel; Neely, Michael N; Strojil, Jan

    2017-03-01

    Monte Carlo simulations allow prediction and comparison of concentration-time profiles arising from different dosing regimens in a defined population, provided a population pharmacokinetic model has been established. The aims of this study were to evaluate the population pharmacokinetics of imipenem in critically ill patients with hospital-acquired pneumonia (HAP) and to assess the probability of target attainment (PTA) and cumulative fraction of response (CFR) using EUCAST data. A two-compartment model based on a data set of 19 subjects was employed. Various dosage regimens at 0.5-h and 3-h infusion rates and as continuous infusion were evaluated against the pharmacodynamic targets of 20%fT>MIC, 40%fT>MIC and 100%fT>MIC. For the target of 40%fT>MIC, all 0.5-h infusion regimens achieved optimal exposures (CFR ≥ 90%) against Escherichia coli and Staphylococcus aureus, with nearly optimal exposure against Klebsiella pneumoniae (CFR ≥ 89.4%). The 3-h infusions and continuous infusion exceeded 97% CFR against all pathogens with the exception of Pseudomonas aeruginosa and Acinetobacter spp., where the maximum CFRs were 85.5% and 88.4%, respectively. For the 100%fT>MIC target, only continuous infusion was associated with nearly optimal exposures. Higher PTAs for the targets of 40%fT>MIC and 100%fT>MIC were achieved with 3-h infusions and continuous infusion in comparison with 0.5-h infusions; however, continuous infusion carries a risk of not reaching the MIC of less susceptible pathogens in a higher proportion of patients. In critically ill patients with HAP with risk factors for Gram-negative non-fermenting bacteria, maximum doses administered as extended infusions may be necessary.

  13. Effects on nutrient and hormonal profile of long-term infusions of glucose or insulin plus glucose in cows treated with recombinant bovine somatotropin before peak milk yield.

    PubMed

    Léonard, M; Block, E

    1997-01-01

    Ten Holstein cows were treated with 30.9 mg.d-1 of recombinant bST from 15 to 41 d of lactation. The Latin square design included three infusion periods of 6 d each with 3 d of rest between infusion periods. Infusions were physiological saline, glucose (50 g.h-1), and insulin plus glucose (12.5 IU.h-1 + 50 g.h-1). Blood was collected continuously during the last 24 h of each infusion period. Statistical analyses of data for energy balance, milk yield, and DMI were performed on the last 3 d of each infusion period. Production data before and after infusions (i.e., no recombinant bST) estimated that recombinant bST increased milk yield of cows infused with glucose and saline by 3.1 and 3.6 kg.d-1, respectively. Net energy intake was not affected by infusion, but glucose infusion resulted in higher BW loss than did saline infusion (2.33 vs. 0.08 kg.d-1, respectively), and insulin plus glucose infusion resulted in BW gain (0.65 kg.d-1). Milk yield was 39.9, 39.6, and 37.6 kg.d-1 for cows infused with saline, glucose, and insulin plus glucose, respectively. The insulin plus glucose infusion increased milk protein 11 and 14% compared with response to saline and glucose infusions, respectively; no change occurred in the proportion of casein and whey proteins. Serum bST was increased 109% with exogenous recombinant bST. Serum IGF-I was lower for cows infused with glucose than for those infused with saline (21.03 vs. 27.44 ng.ml-1) and increased to 46.55 ng.ml-1 for cows infused with insulin plus glucose. Serum concentrations of insulin and glucose were 13.7 and 56.7, 18.5 and 61.9, and 30.5 muIU.ml-1 and 39.4 mg.dl-1 for cows infused with saline, glucose, and insulin plus glucose, respectively. The results of this study suggest that low concentrations of plasma insulin in early lactation may limit the IGF-I response to recombinant bST (uncoupling). Despite higher IGF-I, milk yield was lower, probably as a result of low blood glucose. These results suggest that, in early

  14. Acceleration of insulin pharmacodynamic profile by a novel insulin infusion site warming device.

    PubMed

    Cengiz, Eda; Weinzimer, Stuart A; Sherr, Jennifer L; Tichy, Eileen; Martin, Melody; Carria, Lori; Steffen, Amy; Tamborlane, William V

    2013-05-01

    Subcutaneously injected rapid-acting insulin analogs do not replicate physiologic insulin action due to delays in their onset and peak action resulting in postprandial glucose excursions. The InsuPatch (IP) is a novel insulin infusion site warming device developed to accelerate insulin action by increasing blood flow to the area of insulin absorption. Thirteen adolescents with type 1 diabetes (T1D, mean age 14 ± 4 yr) were enrolled in this study to investigate the effect of the IP on the pharmacodynamics and pharmacokinetics of a 0.2 unit/kg bolus dose of aspart insulin using the euglycemic clamp technique. Each subject underwent two euglycemic clamp procedures on separate occasions: one with IP and one without IP activation in random order. When the insulin bolus was given with IP activation as compared to without IP activation, time to reach maximum insulin action (T(GIRmax)) and to reach 50% maximum action (T(50%GIRmax)) were 35 and 18 min earlier (125 ± 8 min vs. 90 ± 6 min, p = 0.002 and 58 ± 5 min. vs. 40 ± 3 min, p = 0.01, respectively), and the area under curve, AUC(GIR 0-90 min), reflecting early glucodynamic action, was significantly greater (p = 0.001). IP activation also accelerated the rise in plasma insulin levels after the bolus (p = 0.03) and resulted in a higher peak (p = 0.04) and greater overall increase (p = 0.02) in plasma insulin levels. Our results show that insulin infusion site warming with IP activation accelerates the time action profile of aspart insulin which may be of benefit to current open-loop and future closed-loop insulin delivery in patients with T1D. © 2012 John Wiley & Sons A/S.

  15. Continuous Glucose Monitoring Enables the Detection of Losses in Infusion Set Actuation (LISAs).

    PubMed

    Howsmon, Daniel P; Cameron, Faye; Baysal, Nihat; Ly, Trang T; Forlenza, Gregory P; Maahs, David M; Buckingham, Bruce A; Hahn, Juergen; Bequette, B Wayne

    2017-01-15

    Reliable continuous glucose monitoring (CGM) enables a variety of advanced technology for the treatment of type 1 diabetes. In addition to artificial pancreas algorithms that use CGM to automate continuous subcutaneous insulin infusion (CSII), CGM can also inform fault detection algorithms that alert patients to problems in CGM or CSII. Losses in infusion set actuation (LISAs) can adversely affect clinical outcomes, resulting in hyperglycemia due to impaired insulin delivery. Prolonged hyperglycemia may lead to diabetic ketoacidosis-a serious metabolic complication in type 1 diabetes. Therefore, an algorithm for the detection of LISAs based on CGM and CSII signals was developed to improve patient safety. The LISA detection algorithm is trained retrospectively on data from 62 infusion set insertions from 20 patients. The algorithm collects glucose and insulin data, and computes relevant fault metrics over two different sliding windows; an alarm sounds when these fault metrics are exceeded. With the chosen algorithm parameters, the LISA detection strategy achieved a sensitivity of 71.8% and issued 0.28 false positives per day on the training data. Validation on two independent data sets confirmed that similar performance is seen on data that was not used for training. The developed algorithm is able to effectively alert patients to possible infusion set failures in open-loop scenarios, with limited evidence of its extension to closed-loop scenarios.

  16. Continuous Glucose Monitoring Enables the Detection of Losses in Infusion Set Actuation (LISAs)

    PubMed Central

    Howsmon, Daniel P.; Cameron, Faye; Baysal, Nihat; Ly, Trang T.; Forlenza, Gregory P.; Maahs, David M.; Buckingham, Bruce A.; Hahn, Juergen; Bequette, B. Wayne

    2017-01-01

    Reliable continuous glucose monitoring (CGM) enables a variety of advanced technology for the treatment of type 1 diabetes. In addition to artificial pancreas algorithms that use CGM to automate continuous subcutaneous insulin infusion (CSII), CGM can also inform fault detection algorithms that alert patients to problems in CGM or CSII. Losses in infusion set actuation (LISAs) can adversely affect clinical outcomes, resulting in hyperglycemia due to impaired insulin delivery. Prolonged hyperglycemia may lead to diabetic ketoacidosis—a serious metabolic complication in type 1 diabetes. Therefore, an algorithm for the detection of LISAs based on CGM and CSII signals was developed to improve patient safety. The LISA detection algorithm is trained retrospectively on data from 62 infusion set insertions from 20 patients. The algorithm collects glucose and insulin data, and computes relevant fault metrics over two different sliding windows; an alarm sounds when these fault metrics are exceeded. With the chosen algorithm parameters, the LISA detection strategy achieved a sensitivity of 71.8% and issued 0.28 false positives per day on the training data. Validation on two independent data sets confirmed that similar performance is seen on data that was not used for training. The developed algorithm is able to effectively alert patients to possible infusion set failures in open-loop scenarios, with limited evidence of its extension to closed-loop scenarios. PMID:28098839

  17. Changes in fetal mannose and other carbohydrates induced by a maternal insulin infusion in pregnant sheep.

    PubMed

    Brown, Laura D; Thorn, Stephanie R; Cheung, Alex; Lavezzi, Jinny R; Battaglia, Frederick C; Rozance, Paul J

    2014-01-01

    The importance of non-glucose carbohydrates, especially mannose and inositol, for normal development is increasingly recognized. Whether pregnancies complicated by abnormal glucose transfer to the fetus also affect the regulation of non-glucose carbohydrates is unknown. In pregnant sheep, maternal insulin infusions were used to reduce glucose supply to the fetus for both short (2-wk) and long (8-wk) durations to test the hypothesis that a maternal insulin infusion would suppress fetal mannose and inositol concentrations. We also used direct fetal insulin infusions (1-wk hyperinsulinemic-isoglycemic clamp) to determine the relative importance of fetal glucose and insulin for regulating non-glucose carbohydrates. A maternal insulin infusion resulted in lower maternal (50%, P < 0.01) and fetal (35-45%, P < 0.01) mannose concentrations, which were highly correlated (r(2) = 0.69, P < 0.01). A fetal insulin infusion resulted in a 50% reduction of fetal mannose (P < 0.05). Neither maternal nor fetal plasma inositol changed with exogenous insulin infusions. Additionally, maternal insulin infusion resulted in lower fetal sorbitol and fructose (P < 0.01). Chronically decreased glucose supply to the fetus as well as fetal hyperinsulinemia both reduce fetal non-glucose carbohydrates. Given the role of these carbohydrates in protein glycosylation and lipid production, more research on their metabolism in pregnancies complicated by abnormal glucose metabolism is clearly warranted.

  18. Efficacy evaluation of syringe pump developed for continuous drug infusion

    PubMed Central

    Jung, Bongsu; Seo, Kwang-Suk; Kwon, Suk Jin; Lee, Kiyoung; Hong, Suyong; Seo, Hyounsoon; Kim, Gi-Young; Park, Geun-Mook; Jeong, Juhee

    2016-01-01

    Background In dental intravenous sedation, continuous intravenous infusion of a low-dose drug requires an infusion pump such as a syringe pump. To develop a new syringe pump for clinical use, the functions of the pump must meet certain international standards. Various safety and efficacy tests must be performed on the syringe pump, as stipulated by these standards, and an approval must be received from the approving agency based on such test results. Methods The authors of the present study developed a novel syringe pump and performed efficacy evaluation by testing its infusion speed at 1 and 25 ml/h, and infusion performance testing at 2 and 24 h. Moreover, performance evaluation was conducted by comparing the novel pump to an existing pump with the infusion speed varied from 1 to 5 ml/h. Results In the efficacy testing on the newly developed syringe pump, infusion with the infusion speed initially set to 1 ml/h resulted in infusion speeds of 1.00 and 0.99 ml/h in the 2- and 24-h assessment, respectively. Changing the infusion speed setting to 25 ml/h resulted in an infusion speed of 25.09 and 23.92 ml/h in the 2- and 24-h assessment, respectively. These results show no significant differences when compared with other commercially available pumps. Conclusions The efficacy testing of the newly developed syringe pump showed the accuracy to be within tolerance. Based on these findings, we believe that the newly developed syringe pump is suitable for clinical use. PMID:28879319

  19. The effect of insulin infusion and food intake on muscle protein synthesis in postabsorptive rats.

    PubMed Central

    Garlick, P J; Fern, M; Preedy, V R

    1983-01-01

    1. Insulin was infused into young male rats in the postabsorptive state. Rates of protein synthesis in skeletal muscle were determined during the final 10 min of infusion from the incorporation of label into protein after intravenous injection of a massive dose of [3H]phenylalanine. Rates of synthesis were not altered during the first 10 min of insulin infusion, but were increased significantly between 10 and 60 min. 2. Rats were infused with different amounts of insulin for 30 min. When concentrations were increased from 10 to 40 microunits/ml of plasma there was no change in muscle protein synthesis, but concentrations higher than 70 microunits/ml caused a significant stimulation. Concentrations below 10 microunits/ml, obtained by infusion of anti-insulin serum, did not depress synthesis below that found in the postabsorptive rat. 3. Infusion of glucose for 30 or 60 min led to an increase in plasma insulin to 40 microunits/ml, but this also failed to stimulate muscle protein synthesis. 4. Rates of synthesis in postabsorptive rats, even when stimulated maximally by insulin, were not so high as those in fed rats or in postabsorptive rats refed for 60 min. However, in fed and refed rats insulin concentrations were below that required to stimulate synthesis in postabsorptive animals. Despite this, infusion of large amounts of insulin into fed rats did not increase synthesis further. 5. The sensitivity of plasma glucose to insulin infusion was different from that of protein synthesis. A decrease in glucose concentration preceded the increase in synthesis and occurred at lower insulin concentrations. 6. It is concluded that changes in circulating insulin may have been partly responsible for the increase in muscle protein synthesis brought about by feeding, but that other factors must also play a part. PMID:6347182

  20. Continuous ampicillin infusion as an alternative to intermittent infusion for adult inpatients: a case series.

    PubMed

    Ogawa, Taku; Kasahara, Kei; Ikawa, Kazuro; Shigeta, Junichi; Komatsu, Yuko; Kuruno, Noriko; Uno, Kenji; Maeda, Koichi; Mikasa, Keiichi

    2014-10-01

    Intravenous ampicillin has been extensively used for various kinds of infections for more than fifty years. This drug is administered intermittently, which can result in missed or delayed drug administration and sleep interruption that can have a negative impact on the quality of life during hospitalization. Continuous infusion may solve these concerns. We reviewed the cases of five patients who were treated with continuous ampicillin infusions in our hospital. The ampicillin serum concentrations were from 11.3 to 32.8 μg/mL, which was above the ampicillin MICs of the causative organisms, ≤0.06 to 4 μg/mL. Although the dosages given of ampicillin varied in each case, the serum concentrations showed a strong correlation with creatinine clearance (r(2) = 0.91). All the patients improved at the time of discharge, or transfer to another hospital, with no significant complications during the continuous infusion. Continuous ampicillin infusion could be a better alternative for frequent intermittent infusion for adult inpatients with infections due to ampicillin-susceptible organisms.

  1. Insulin secretion and cellular glucose metabolism after prolonged low-grade intralipid infusion in young men.

    PubMed

    Jensen, Christine B; Storgaard, Heidi; Holst, Jens J; Dela, Flemming; Madsbad, Sten; Vaag, Allan A

    2003-06-01

    We examined the simultaneous effects of a 24-h low-grade Intralipid infusion on peripheral glucose disposal, intracellular glucose partitioning and insulin secretion rates in twenty young men, by 2-step hyperinsulinemic euglycemic clamp [low insulin clamp (LI), 10 mU/m(2) x min; high insulin clamp (HI), 40 mU/m(2) x min], 3-(3)H-glucose, indirect calorimetry, and iv glucose tolerance test. Free fatty acid concentrations were similar during basal steady state but 3.7- to 13-fold higher during clamps. P-glucagon increased and the insulin/glucagon ratio decreased at both LI and HI during Intralipid infusion. At LI, glucose oxidation decreased by 10%, whereas glucose disposal, glycolytic flux, glucose storage, and glucose production were not significantly altered. At HI, glucose disposal, and glucose oxidation decreased by 12% and 24%, respectively, during Intralipid infusion. Glycolytic flux, glucose storage, and glucose production were unchanged. Insulin secretion rates increased in response to Intralipid infusion, but disposition indices (DI = insulin action.insulin secretion) were unchanged. In conclusion, a 24-h low-grade Intralipid infusion caused insulin resistance in the oxidative (but not in the nonoxidative) glucose metabolism in young healthy men. Moreover, insulin hypersecretion perfectly countered the free-fatty acid-induced insulin resistance. Future studies are needed to determine the role of a prolonged moderate lipid load in subjects at increased risk of developing diabetes.

  2. Insulin/glucose infusion successfully resuscitates bupivacaine-induced sudden-onset circulatory collapse in dogs.

    PubMed

    Kim, Mi-Hyun; Lee, Kook-Hyun; Kim, Chong-Soo; Yang, Solmon; Uugangerel, Teserendorj; Kim, Chong-Min; Kang, Byeong-Chul

    2013-05-01

    In previous studies, insulin reversed the cardiac toxicity gradually induced by a continuous infusion of bupivacaine. In this randomized controlled study, we intended to simulate a more relevant clinical situation by injecting bupivacaine rapidly as a bolus to induce sudden-onset circulatory collapse in dogs. We then evaluated the insulin effect. Bupivacaine (10 mg.kg(-1) iv) was rapidly administered intravenously to 12 dogs. At the onset of circulatory collapse (defined as a mean arterial pressure [MAP] of 30 mmHg), external chest compression was initiated. Insulin (2 U.kg(-1) iv) was given to the insulin-glucose (IG) group (n = 6) and the same volume of 0.9% saline was given to the control (C) group (n = 6). The primary outcome was successful resuscitation defined as both MAP ≥ 60 mmHg and sinus rhythm on an electrocardiogram that lasted ≥ 60 sec. Hemodynamic and blood variables were measured, including cardiac output and electrocardiogram intervals. All IG dogs were successfully resuscitated within 15 (3) min, whereas none of the control dogs were resuscitated (P = 0.002). After circulatory collapse, the average MAP was higher in group IG than in group C (P = 0.006). Insulin effectively reversed the sudden-onset circulatory collapse in dogs caused by an intravenous bolus injection of bupivacaine.

  3. [Reflections on betalactam antibiotics administered by continuous infusion].

    PubMed

    López, Ester; Soy, Dolors; Miana, M Teresa; Codina, Carles; Ribas, Josep

    2006-01-01

    Numerous studies on continuous intravenous infusion of betalactam antibiotics have indicated that this could be a useful strategy for treating nosocomial infections as well as exacerbations of pulmonary infections in patients with cystic fibrosis and episodes of febrile neutropenia. From the pharmacodynamic viewpoint, betalactam antibiotics have a time-dependent behavior. Thus, the pharmacokinetic/pharmacodynamic index that best correlates with therapeutic efficacy appears to be the time during which free antibiotic concentrations remain above the minimum inhibitory concentration (MIC) of the infecting microorganism. Continuous infusion of betalactams successfully optimizes this pharmacokinetic/ pharmacodynamic index. Furthermore, some studies have shown that this therapeutic strategy may be favorable economically.

  4. Continuous infusion of factor VIII for surgery and major bleeding.

    PubMed

    Hay, C R; Doughty, H I; Savidge, G F

    1996-03-01

    In a clinical trial, 24 patients with haemophilia A who needed surgery or had suffered severe bleeding were treated by continuous infusion of Monoclate P, a factor VIII concentrate that is immunopurified by monoclonal antibodies. Continuous infusion of Monoclate P began with a dose of 2 U/kg per h that was adjusted according to the results of factor VIII assays to achieve a factor VIII target level of 100 IU/dl for 2 days and then 80 IU/dl for 5 days. The safety, efficacy, and economics of this approach were assessed. No haemorrhagic episodes were observed. The continuous infusion was convenient and had the advantage of producing steady-state levels of factor VIII. With a single-compartment model, we found median factor VIII clearance values of 3.11 (range 1.79-7.78) x 10(3) litres/kg per h, elimination rates of 5.0-19.4 x 10(-2)/h and a median half-life of 9.9 h (range 4.8-20.0 h). Clearance and the elimination rate appeared to decline over the infusion period, as judged by the decreasing infusion rate required to maintain the target concentration of factor VIII. An economic comparison with bolus therapy, using theoretically derived bolus dosages, indicated that the potential saving was related inversely to the factor VIII half-life. Potential savings of 75% were predicted on the first postoperative day, averaging 35% over the full course of therapy.

  5. Continuous intravenous infusions of bromodeoxyuridine as a clinical radiosensitizer

    SciTech Connect

    Kinsella, T.J.; Mitchell, J.B.; Russo, A.; Aiken, M.; Morstyn, G.; Hsu, S.M.; Rowland, J.; Glatstein, E.

    1984-10-01

    Twelve patients were treated with continuous intravenous (24-hour) infusions of bromodeoxyuridine (BUdR) at 650 or 1000 mg/m2/d for up to two weeks. Myelosuppression, especially thrombocytopenia, was the major systemic toxicity and limited the infusion period to nine to 14 days. However, bone marrow recovery occurred within seven to ten days, allowing for a second infusion in most patients. Local toxicity (within the radiation field) was minimal, with the exception of one of four patients, who underwent abdominal irradiation. Pharmacology studies revealed a steady-state arterial plasma level of 6 x 10(-7) mol/L and 1 x 10(-6) mol/L during infusion of 650 and 1000 mg/m2/d, respectively. In vivo BUdR uptake into normal bone marrow was evaluated in two patients by comparison of preinfusion and postinfusion in vitro radiation survival curves of marrow CFUc with enhancement ratios (D0-pre/D0-post) of 1.8 (with 650 mg/m2/d) and 2.5 (with 1000 mg/m2/d). In vivo BUdR incorporation into normal skin and tumor cells using an anti-BUdR monoclonal antibody and immunohistochemistry was demonstrated in biopsies from three patients revealing substantially less cellular incorporation into normal skin (less than 10%) compared with tumor (up to 50% to 70%). The authors conclude that local and systemic toxicity of continuous infusion of BUdR at 1000 mg/m2/d for approximately two weeks is tolerable. The observed normal tissue toxicity is comparable with previous clinical experience with intermittent (12 hours every day for two weeks) infusions of BUdR. Theoretically, a constant infusion should allow for greater incorporation of BUdR into cycling tumor cells and thus, for further enhancement of radiosensitization.

  6. [Treatment of diabetic ketoacidosis and hyperosmolality with low dose insulin infusion (author's transl)].

    PubMed

    Duclos, F; François, P; Dumon, P; Altmann, J J

    1978-06-03

    Fifteen patients were treated with low-dose (5 u/hour) insulin infusion, including 10 cases of ketoacidosis, 3 cases of hyperglycemia without acidosis in severely affected diabetics, and 2 cases with hyperosmolality. The treatment was successful in all cases. Insulin was infused at a constant rate, during 12 hours as a mean value. Blood glucose fell regularly and no hypoglycemia occured. Serum potassium varied within narrow limits, and no accident related to hypokalemia was observed. The correction of ketoacidosis was delayed, as compared to that of hyperglycemia. The two elderly patients with hyperosmolality recovered quickly and completely. The method of low-dose insulin infusion seems thus effective and easily applicable, at least in an intensive care unit. Our experience prompted us to increase (10 u/h) rather than to decrease the insulin infusion rate, with the aim to obtain a faster correction of ketoacidosis.

  7. Continuous infusion of enzyme replacement therapy is inferior to weekly infusions in MPS I dogs

    PubMed Central

    Passage, M.B.; Krieger, A.W.; Peinovich, M.C.; Lester, T.; Le, S.Q.; Dickson, P.I.; Kakkis, E.D.

    2010-01-01

    Summary Intravenous enzyme replacement therapy with recombinant human α-l-iduronidase (rhIDU) is used weekly to treat mucopolysaccharidosis (MPS) I. We tested continuous administration of rhIDU at two dosing levels (0.58 mg/kg/week and 2 mg/kg/week) in MPS I dogs, and compared the efficacy of continuous to the clinically-used 0.58 mg/kg weekly three-hour infusion. Peak plasma concentrations of rhIDU were much higher in weekly-treated dogs (mean 256 units/ml) than steady-state concentrations in dogs treated with continuous infusion (mean 1.97 units/ml at 0.58 mg/kg/week; 10.1 units/ml at 2 mg/kg/week). Dogs receiving continuous IV rhIDU, even at a higher (2 mg/kg/week) dose, had consistently lower iduronidase levels in tissues than dogs receiving a weekly (0.58 mg/kg/week) dose. GAG storage was also less improved by continuous intravenous infusion. Adverse events were similar in all dosing groups. We found that continuous administration of 2 mg/kg/week rhIDU to MPS I dogs was insufficient to achieve GAG storage reduction comparable to 0.58 mg/kg weekly dosing. PMID:19562502

  8. Effects of intravenous lipopolysaccharide infusion on glucose and insulin dynamics in horses with equine metabolic syndrome.

    PubMed

    Tadros, Elizabeth M; Frank, Nicholas; De Witte, Fiamma Gomez; Boston, Raymond C

    2013-07-01

    To test the hypothesis that glucose and insulin dynamics during endotoxemia differ between healthy horses and horses with equine metabolic syndrome (EMS). 6 healthy adult mares and 6 horses with EMS. Each horse randomly received an IV infusion of lipopolysaccharide (20 ng/kg [in 60 mL of sterile saline {0.9% NaCl} solution]) or saline solution, followed by the other treatment after a 7-day washout period. Baseline insulin-modified frequently sampled IV glucose tolerance tests were performed 27 hours before and then repeated at 0.5 and 21 hours after infusion. Results were assessed via minimal model analysis and area under the curve values for plasma glucose and serum insulin concentrations. Lipopolysaccharide infusion decreased insulin sensitivity and increased area under the serum insulin concentration curve (treatment × time) in both healthy and EMS-affected horses, compared with findings following saline solution administration. The magnitude of increase in area under the plasma glucose curve following LPS administration was greater for the EMS-affected horses than it was for the healthy horses. Horses with EMS that received LPS or saline solution infusions had decreased insulin sensitivity over time. Glucose and insulin responses to endotoxemia differed between healthy horses and horses with EMS, with greater loss of glycemic control in EMS-affected horses. Horses with EMS also had greater derangements in glucose and insulin homeostasis that were potentially stress induced. It may therefore be helpful to avoid exposure of these horses to stressful situations.

  9. Continuous low-dose fructose infusion does not reverse glucagon-mediated decrease in hepatic glucose utilization.

    PubMed

    Johnson, Paulette M; Chen, Sheng-Song; Santomango, Tammy S; Williams, Phillip E; Lacy, D Brooks; McGuinness, Owen P

    2011-06-01

    An adaptation to continuous total parenteral nutrition (TPN; 75% of nonprotein calories as glucose) is the liver becomes a major consumer of glucose with lactate release as a by-product. The liver is able to further increase liver glucose uptake when a small dose of fructose is acutely infused via the portal system. Glucagon, commonly elevated during inflammatory stress, is a potent inhibitor of glucose uptake by the liver during TPN. The aim was to determine if continuous fructose infusion could overcome the glucagon-mediated decrease in hepatic glucose uptake. Studies were performed in conscious, insulin-treated, chronically catheterized, pancreatectomized dogs that adapted to TPN for 33 hours. They were then assigned to 1 of 4 groups: TPN (C), TPN + fructose (4.4 μmol kg(-1) min(-1); F), TPN + glucagon (0.2 pmol kg(-1) min(-1); GGN), or TPN + fructose and glucagon (F + GGN) for an additional 63 hours (33-96 hours). Insulin, fructose, and glucagon were infused into the portal vein. During that period, all animals received a fixed insulin infusion of 0.4 mU·kg(-1)·min(-1) (33-96 hours); and the glucose infusion rates were adjusted to maintain euglycemia (6.6 mmol/L). Continuous fructose infusion was unable to further enhance net hepatic glucose uptake (in micromoles per kilogram per minute) (31.1 ± 2.8 vs 36.1 ± 5.0; C vs F), nor was it able to overcome glucagon-mediated decrease in net hepatic glucose uptake (10.0 ± 4.4 vs 12.2 ± 3.9; GGN vs F + GGN). In summary, continuous fructose infusion cannot augment liver glucose uptake during TPN; nor can it overcome the inhibitory effects of glucagon. Copyright © 2011 Elsevier Inc. All rights reserved.

  10. Electronic flow rate controller for a portable insulin infusion pump.

    PubMed

    Ferguson, R T; Zinman, B; Marliss, E B; Albisser, A M

    1980-01-01

    An electronic controller is described that regulates the flow of infusate by controlling the fraction of time that a pump is energized. Using the integral programming capability of the device, any one of 256 possible basal rates between 0 and 49.6% of the maximum rate can be chosen. An externally triggerable single meal-associated pulse can also be configured. The rate during the meal pulse can be any one of the 255 equally spaced rates in the range of 0--99.7%. The duration of this pulse can be chosen in 3-min steps to a maximum of 12.75 h, after which the rate automatically returns to the basal value. The controller consumes a minimum amount of power and can continuously operate a dc motor-driven pump at 3.0 V for 36 h. It drives the pump in an on-off mode in order to control the average flow rate digitally. In this way a significant reduction in the power requirements is realized and the system can be run for many days using small rechargeable batteries. One year of experience with 20 of these controllers was obtained in the research laboratory and clinical investigation unit. The results of this experience indicated the reliability and precision of these controllers, gave insight into their modes of failure, and provided valuable biomedical data for their improvement.

  11. Regional blood flow during continuous low-dose endotoxin infusion

    SciTech Connect

    Fish, R.E.; Lang, C.H.; Spitzer, J.A.

    1986-01-01

    Escherichia coli endotoxin (ET) was administered to adult rats by continuous IV infusion from a subcutaneously implanted osmotic pump (Alzet). Cardiac output and regional blood flow were determined by the radiolabeled microsphere method after 6 and 30 hr of ET or saline infusion. Cardiac output (CO) of ET rats was not different from time-matched controls, whereas arterial pressure was 13% lower after 30 hr of infusion. After both 6 and 30 hr of ET, pancreatic blood flow and percentage of cardiac output were lower than in controls. Estimated portal venous flow was decreased at each time point, and an increased hepatic arterial flow (significant after 30 hr) resulted in an unchanged total hepatic blood flow. Blood flow to most other tissues, including epididymal fat, muscle, kidneys, adrenals, and gastrointestinal tract, was similar between treatments. Maintenance of blood flow to metabolically important tissues indicates that the previously reported alterations in in vitro cellular metabolism are not due to tissue hypoperfusion. Earlier observations of in vitro myocardial dysfunction, coexistent with the significant impairment in pancreatic flow, raise the possibility that release of a myocardial depressant factor occurs not only in profound shock but also under less severe conditions of sepsis and endotoxemia.

  12. Epidural Analgesia for Labor: Continuous Infusion Versus Programmed Intermittent Bolus.

    PubMed

    Onuoha, Onyi C

    2017-03-01

    Despite the traditional practice to maintain labor analgesia with a combination of continuous epidural infusion and patient-controlled epidural analgesia using an automated epidural pump; compelling data now shows that bolus injection through the epidural catheter may result in better distribution of anesthetic solution in the epidural space. The programmed intermittent epidural bolus technique is proposed as a better maintenance mode and may represent a more effective mode of maintaining epidural analgesia for labor, especially prolonged labor. Additional prospective and adequately powered studies are needed to confirm findings and determine the optimal combination of volume, rate, time, and drug concentration. Copyright © 2016 Elsevier Inc. All rights reserved.

  13. Novel therapy for insulin-dependent diabetes mellitus: infusion of in vitro-generated insulin-secreting cells.

    PubMed

    Dave, S D; Vanikar, A V; Trivedi, H L; Thakkar, U G; Gopal, S C; Chandra, T

    2015-02-01

    Insulin-dependent diabetes mellitus (IDDM) is a metabolic disease usually resulting from autoimmune-mediated β-cell destruction requiring lifetime exogenous insulin replacement. Mesenchymal stem cells (MSC) hold promising therapy. We present our experience of treating IDDM with co-infusion of in vitro autologous adipose tissue-derived MSC-differentiated insulin-secreting cells (ISC) with hematopoietic stem cells (HSC). This was an Institutional Review Board approved prospective non-randomized open-labeled clinical trial after informed consent from ten patients. ISC were differentiated from autologous adipose tissue-derived MSC and were infused with bone marrow-derived HSC in portal, thymic circulation by mini-laparotomy and in subcutaneous circulation. Patients were monitored for blood sugar levels, serum C-peptide levels, glycosylated hemoglobin (Hb1Ac) and glutamic acid decarboxylase (GAD) antibodies. Insulin administration was made on sliding scale with an objective of maintaining FBS < 150 mg/dL and PPBS around 200 mg/dL. Mean 3.34 mL cell inoculums with 5.25 × 10(4) cells/μL were infused. No untoward effects were observed. Over a mean follow-up of 31.71 months, mean serum C-peptide of 0.22 ng/mL before infusion had sustained rise of 0.92 ng/mL with decreased exogenous insulin requirement from 63.9 international units (IU)/day to 38.6 IU/day. Improvement in mean Hb1Ac was observed from 10.99 to 6.72%. Mean GAD antibodies were positive in all patients with mean of 331.10 IU/mL, which decreased to mean of 123 IU/mL. Co-infusion of autologous ISC with HSC represents a viable novel therapeutic option for IDDM.

  14. A guideline for the use of variable rate intravenous insulin infusion in medical inpatients.

    PubMed

    George, S; Dale, J; Stanisstreet, D

    2015-06-01

    The present paper summarizes the key recommendations in a recent publication produced by the Joint British Diabetes Societies for Inpatient Care on the use of variable rate i.v. insulin infusion in 'medical' inpatients. The full guideline is available at http://www.diabetologists-abcd.org.uk/JBDS/JBDS_IP_VRIII.pdf and is designed to be a practical guide that can used by any healthcare professional who manages medical inpatients with hyperglycaemia. Its main aim is to allow variable rate i.v. insulin infusion to be used safely, effectively and efficiently for this specific group of inpatients. © 2015 The Authors. Diabetic Medicine © 2015 Diabetes UK.

  15. Combining Basal–Bolus Insulin Infusion for Tight Postprandial Glucose Control: An in Silico Evaluation in Adults, Children, and Adolescents

    PubMed Central

    Revert, Ana; Rossetti, Paolo; Calm, Remei; Vehí, Josep; Bondia, Jorge

    2010-01-01

    Background Achieving good postprandial glycemic control, without triggering hypoglycemia events, is a challenge of treatment strategies for type 1 diabetes subjects. Continuous subcutaneous insulin infusion, the gold standard of therapy, is based on heuristic adjustments of both basal and prandial insulin. Some tools, such as bolus calculators, are available to aid patients in selecting a meal-related insulin dose. However, they are still based on empiric parameters such as the insulin-to-carbohydrate ratio and on the physicians’ and patients’ ability to fit bolus mode to meal composition. Method In this article, a nonheuristic method for assessment of prandial insulin administration is presented and evaluated. An algorithm based on set inversion via interval analysis is used to coordinate basal and bolus insulin infusions to deal with postprandial glucose excursions. The evaluation is carried out through an in silico study using the 30 virtual patients available in the educational version of the Food and Drug Administration-accepted University of Virginia simulator. Results obtained using the standard bolus strategy and different coordinated basal–bolus solutions provided by the algorithm are compared. Results Coordinated basal–bolus solutions improve postprandial glucose performance in most cases, mainly in terms of reducing hypoglycemia risk, but also increasing the percentage of time in normoglycemia. Moreover, glycemic variability is reduced considerably by using these innovative solutions. Conclusions The algorithm presented here is a robust nonheuristic alternative to deal with postprandial glycemic control. It is shown as a powerful tool that could be integrated in future smart insulin pumps. PMID:21129338

  16. Minimum infusion rate and adrenocortical function after continuous infusion of the novel etomidate analog ET-26-HCl in rats.

    PubMed

    Jiang, Junli; Wang, Bin; Zhu, Zhaoqiong; Yang, Jun; Liu, Jin; Zhang, Wensheng

    2017-01-01

    Because etomidate induces prolonged adrenal suppression, even following a single bolus, its use as an infused anesthetic is limited. Our previous study indicated that a single administration of the novel etomidate analog methoxyethyletomidate hydrochloride (ET-26-HCl) shows little suppression of adrenocortical function. The aims of the present study were to (1) determine the minimum infusion rate of ET-26-HCl and compare it with those for etomidate and cyclopropyl-methoxycarbonylmetomidate (CPMM), a rapidly metabolized etomidate analog that is currently in clinical trials and (2) to evaluate adrenocortical function after a continuous infusion of ET-26-HCl as part of a broader study investigating whether this etomidate analog is suitable for long infusion in the maintenance of anesthesia. The up-and-down method was used to determine the minimum infusion rates for ET-26-HCl, etomidate and CPMM. Sprague-Dawley rats (n = 32) were then randomly divided into four groups: etomidate, ET-26-HCl, CPMM, and vehicle control. Rats in each group were infused for 60 min with one of the drugs at its predetermined minimum infusion rate. Blood samples were drawn initially and then every 30 min after drug infusion to determine the adrenocorticotropic hormone-stimulated concentration of serum corticosterone as a measure of adrenocortical function. The minimum infusion rates for etomidate, ET-26-HCl and CPMM were 0.29, 0.62, and 0.95 mg/kg/min, respectively. Compared with controls, etomidate decreased serum corticosterone, as expected, whereas serum corticosterone concentrations following infusion with the etomidate analogs ET-26-HCl or CPMM were not significantly different from those in the control group. The corticosterone concentrations tended to be reduced for the first hour following ET-26-HCl infusion (as compared to vehicle infusion); however, this reduction did not reach statistical significance. Thus, further studies are warranted examining the practicability of using ET-26

  17. [Insulin therapy by insulin pump: continuous or conventional self-blood glucose monitoring? ].

    PubMed

    Renard, E

    2003-04-01

    Use of portable pumps is increasing to achieve intensive insulin treatment. Beside unpredictable insulin absorption and insufficient reactivity to changes of insulin flow rate due to the subcutaneous route, this therapy is however limited by the lack of information on blood glucose level provided by self-blood glucose monitoring. Thus, patient interpretation only leads to speculative adaptation of pump flow rate. The lack of alert toward the risk of hypoglycemia or hyperglycemic ketogenic deviations can lead to the occurrence of deleterious metabolic distorsions, among which severe hypoglycemia stands in first rank. Starting experiences of continuous recording of interstitial glucose level by portable systems using glucose-oxidase allow on short time durations the identification of daily periods of poor metabolic control. Retrospective availability of information gives the possibility of more adequate treatment adaptations than conventional capillary blood glucose monitoring, but does not allow immediate prevention of metabolic events. Only devices providing real time or near-real time information to the patient can fulfill this function. However, the absence of tight parallelism between variations of interstitial and blood glucose levels may lead to erroneous decisions. A true continuous real time information on blood glucose level on long-term seems only expectable from implantable glucose sensors. Still under investigation, these systems should be able to insure vigilance toward the risk of hypo- and hyperglycemia on weekly or monthly periods. Initially used as complementary to capillary self-monitoring, their reliability should allow their use as substitutes for conventional monitoring, except for measurements aimed at signal calibration. Pump control by the sensor signal is conceivable if it corresponds to a direct, continuous, real time measurement of blood glucose, and subject to a simultaneous improvement of insulin infusion modes.

  18. Continuous infusion of antibiotics in critically ill patients.

    PubMed

    Smuszkiewicz, Piotr; Szałek, Edyta; Tomczak, Hanna; Grześkowiak, Edmund

    2013-02-01

    Antibiotics are the most commonly used drugs in intensive care unit patients and their supply should be based on pharmacokinetic/pharmacodynamic rules. The changes that occur in septic patients who are critically ill may be responsible for subtherapeutic antibiotic concentrations leading to poorer clinical outcomes. Evolving in time the disturbed pathophysiology in severe sepsis (high cardiac output, glomerular hyperfiltration) and therapeutic interventions (e.g. haemodynamically active drugs, mechanical ventilation, renal replacement therapy) alters antibiotic pharmacokinetics mainly through an increase in the volume of distribution and altered drug clearance. The lack of new and efficacious drugs and increased bacterial resistance are current problems of contemporary antibiotic therapy. Although intermittent administration is a standard clinical practice, alternative methods of antibiotic administration are sought, which may potentialise effects and reduce toxicity as well as contribute to inhibition of bacterial resistance. A wide range of studies prove that the application of continuous infusion of time-dependent antibiotics (beta-lactams, glycopeptides) is more rational than standard intermittent administration. However, there are also studies which do not confirm the advantage of one method over the other. In spite of controversy the continuous administration of this group of antibiotics is common practice, because the results of both studies point to the higher efficacy of this method in critically ill patients. Authors reviewed the literature to determine whether any clinical benefits exist for administration of time-dependent antibiotics by continuous infusion. Definite specification of the clinical advantage of administration this way over standard dosage requires a large-scale multi-centre randomised controlled trial.

  19. The regulatory system for diabetes mellitus: Modeling rates of glucose infusions and insulin injections

    NASA Astrophysics Data System (ADS)

    Yang, Jin; Tang, Sanyi; Cheke, Robert A.

    2016-08-01

    Novel mathematical models with open and closed-loop control for type 1 or type 2 diabetes mellitus were developed to improve understanding of the glucose-insulin regulatory system. A hybrid impulsive glucose-insulin model with different frequencies of glucose infusions and insulin injections was analyzed, and the existence and uniqueness of the positive periodic solution for type 1 diabetes, which is globally asymptotically stable, was studied analytically. Moreover, permanence of the system for type 2 diabetes was demonstrated which showed that the glucose concentration level is uniformly bounded above and below. To investigate how to prevent hyperinsulinemia and hyperglycemia being caused by this system, we developed a model involving periodic intakes of glucose with insulin injections applied only when the blood glucose level reached a given critical glucose threshold. In addition, our numerical analysis revealed that the period, the frequency and the dose of glucose infusions and insulin injections are crucial for insulin therapies, and the results provide clinical strategies for insulin-administration practices.

  20. Intravenous infusion of amino acids in dogs attenuates hypothermia during anaesthesia and stimulates insulin secretion.

    PubMed

    Takashima, Satoshi; Shibata, Sanae; Yamada, Kazuto; Ogawa, Mizuho; Nishii, Naohito; Kitagawa, Hitoshi

    2016-07-01

    To evaluate the effect of intravenous infusion of amino acids on the prevention of hypothermia during anaesthesia in dogs. Randomized experimental trial. Seven healthy Beagle dogs. Four concentrations of amino acids were prepared with a 10% amino acid solution and an acetated Ringer's solution, and dogs were infused with each of the solutions at 1 week intervals. Dogs were infused with amino acid solution at 12 mL kg(-1)  hour(-1) for 60 minutes before and for 60 minutes after induction of anaesthesia. Acetated Ringer's solution was infused at the same rate for the remaining 60 minutes of anaesthesia. The infusion treatments were: 1) A0, nutrient-free acetated Ringer's solution; 2) A6, 0.6 g kg(-1)  hour(-1) ; 3) A9, 0.9 g kg(-1)  hour(-1) ; and 4) A12, 1.2 g kg(-1) hour(-1) . Rectal temperature (RT), heart rate (HR), mean arterial pressure (MAP), blood insulin, glucose, urea nitrogen (BUN) and creatinine concentrations, and time to extubation were measured. Before anaesthesia, RT was not affected by amino acid infusion. RT decreased progressively during anaesthesia and the absolute values of RT from 30 to 120 minutes were significantly higher in A12 than in A0 (p < 0.05). Reductions in HR and MAP during anaesthesia were attenuated by amino acid infusion in a dose-dependent manner. Plasma insulin concentration was significantly higher in A12 than in A0 during amino acid infusion and the increase in insulin concentration was greater during than before anaesthesia. BUN increased during amino acid infusion in a dose- and time-dependent fashion. Time until extubation was shorter in A12 than in A0. Amino acids infused at 1.2 g kg(-1)  hour(-1) in dogs attenuated the decrease in RT, HR, and MAP during anaesthesia, and induced a significant increase in plasma insulin concentration. © 2015 Association of Veterinary Anaesthetists and the American College of Veterinary Anesthesia and Analgesia.

  1. Percutaneous catheter-based intracoronary infusion of insulin--a dose finding study in the porcine model.

    PubMed

    Slettom, Grete; Jonassen, Anne K; Tuseth, Vegard; Pettersen, Reidar J; Larsen, Terje H; Seifert, Reinhard; Nordrehaug, Jan E

    2011-06-01

    Insulin given at immediate reperfusion reduces myocardial infarct size in the in vitro and the ex vivo rat heart. In vivo, insulin may cause hypoglycaemia, hypokalaemia and elevation of catecholamines, potentially harmful during an acute myocardial infarction. The purpose of this study was to evaluate tolerance and safety of intracoronary insulin infusions in a porcine model applying percutaneous intervention techniques.

  2. Continuous dopaminergic stimulation achieved by duodenal levodopa infusion.

    PubMed

    Odin, Per; Wolters, Erik; Antonini, Angelo

    2008-12-01

    Continuous dopaminergic stimulation is the ideal approach for the management of Parkinson's disease (PD); this goal can be partially reached with dopamine agonists, but the need for a therapeutic strategy providing a strong and constant dopaminergic stimulation also in the advanced phase of the disease remains unmet. The application of levodopa/carbidopa-gel suspension directly in the duodenum (Duodopa) allows a continuous delivery by a portable pump, resulting in smoother levodopa plasmatic concentrations, and consequently in a physiologic continuous receptor stimulation. Clinical studies have demonstrated that duodenal infusion was associated with significantly better outcome compared to conventional treatment regarding global functioning, ability to walk, "off" time and motor fluctuations. A retrospective analysis of the long-term clinical experience with Duodopa evidenced that daily dose of levodopa decreased by 5% during follow-up. The profile of pharmacological adverse events of Duodopa was similar to that observed with oral administration; dislocation of the intestinal tube to the stomach was the most common technical problem.

  3. Insulin infusion increases levels of free IGF-I and IGFBP-3 proteolytic activity in patients after surgery.

    PubMed

    Nygren, J; Carlsson-Skwirut, C; Brismar, K; Thorell, A; Ljungqvist, O; Bang, P

    2001-10-01

    We have studied the effects of insulin on the bioavailability of insulin-like growth factor (IGF) I in insulin-resistant patients after surgery. Serum levels of total IGF-I (tIGF-I), free IGF (fIGF)-I, fIGF-II, and IGF-binding protein (IGFBP) 1 and IGFBP-3 proteolytic activity (IGFBP-3-PA), determined on the day before surgery and on the 1st postoperative day, were related to insulin sensitivity measured by a hyperinsulinemic, normoglycemic clamp. Before surgery, the decreased tIGF-I (P < 0.05) in response to insulin infusion was accompanied by an 18% reduction of IGFBP-1 (P < 0.001), while IGFBP-3-PA remained unchanged. Levels of fIGF-I and fIGF-II were not changed by insulin infusions. After surgery, IGFBP-3-PA increased (P < 0.05) during insulin infusion, and this was associated with an increase in tIGF-I (P < 0.001) and fIGF-I (P < 0.01), while no significant change was found in fIGF-II. The reduction in IGFBP-1 in response to insulin infusion was not affected by surgery. The change in IGFBP-3-PA during insulin infusion after surgery was related to the corresponding change in fIGF-I (r(2) = 0.26, P < 0.05) and postoperative insulin sensitivity (r(2) = -0.22, P < 0.05). These data suggest that increased IGFBP-3-PA during insulin infusion after surgery governs the increased levels of fIGF-I, while insulin-induced suppression of IGFBP-1 was not affected by surgery. We propose that, in catabolic, postoperative patients, increased levels of insulin from exogenous or, possibly, endogenous sources (nutritionally induced) may be a signal to increase IGF-I bioavailability by increased expression of IGFBP-3-PA to counteract further deterioration in glucose metabolism.

  4. Lipid and insulin infusion-induced skeletal muscle insulin resistance is likely due to metabolic feedback and not changes in IRS-1, Akt, or AS160 phosphorylation.

    PubMed

    Hoy, Andrew J; Brandon, Amanda E; Turner, Nigel; Watt, Matthew J; Bruce, Clinton R; Cooney, Gregory J; Kraegen, Edward W

    2009-07-01

    Type 2 diabetes is characterized by hyperlipidemia, hyperinsulinemia, and insulin resistance. The aim of this study was to investigate whether acute hyperlipidemia-induced insulin resistance in the presence of hyperinsulinemia was due to defective insulin signaling. Hyperinsulinemia (approximately 300 mU/l) with hyperlipidemia or glycerol (control) was produced in cannulated male Wistar rats for 0.5, 1 h, 3 h, or 5 h. The glucose infusion rate required to maintain euglycemia was significantly reduced by 3 h with lipid infusion and was further reduced after 5 h of infusion, with no difference in plasma insulin levels, indicating development of insulin resistance. Consistent with this finding, in vivo skeletal muscle glucose uptake (31%, P < 0.05) and glycogen synthesis rate (38%, P < 0.02) were significantly reduced after 5 h compared with 3 h of lipid infusion. Despite the development of insulin resistance, there was no difference in the phosphorylation state of multiple insulin-signaling intermediates or muscle diacylglyceride and ceramide content over the same time course. However, there was an increase in cumulative exposure to long-chain acyl-CoA (70%) with lipid infusion. Interestingly, although muscle pyruvate dehydrogenase kinase 4 protein content was decreased in hyperinsulinemic glycerol-infused rats, this decrease was blunted in muscle from hyperinsulinemic lipid-infused rats. Decreased pyruvate dehydrogenase complex activity was also observed in lipid- and insulin-infused animals (43%). Overall, these results suggest that acute reductions in muscle glucose metabolism in rats with hyperlipidemia and hyperinsulinemia are more likely a result of substrate competition than a significant early defect in insulin action or signaling.

  5. [Insulin infusion in intensive care: randomized controlled trial].

    PubMed

    Miranda, Milena Penteado Ferraro; Crespo, Jeiel Carlos Lamonica; Secoli, Silvia Regina

    2013-06-01

    This randomized controlled trial compared the use of an intensive and conventional insulin protocol on clinical outcomes in patients with severe sepsis and septic shock, in the first 72 hours. It was conducted at a university hospital in the city of São Paulo. Patients (n=46) were allocated into two groups: intensive glycemic (blood glucose between 80-110mg/dl) and conventional (180-220mg/dl). The Student's t-test and chi-square test were used for data analysis. A statistically significant (p<0.001) difference was observed in mean glycemia, but there was no difference in the variables of mean minimum arterial pressure (p=0.06) or maximum (p=0.11), serum creatinine (p=0,33) or in mortality (p=0.11). Although there was no difference between the groups regarding mortality, hemodynamic instability in the conventional group was longer and the only deaths occurred in it.

  6. Effect of dexamethasone, feeding time, and insulin infusion on leptin concentrations in stallions.

    PubMed

    Cartmill, J A; Thompson, D L; Storer, W A; Crowley, J C; Huff, N K; Waller, C A

    2005-08-01

    Three experiments tested the hypotheses that daily cortisol rhythm, feeding time, and/or insulin infusion affect(s) leptin secretion in stallions. Ten mature stallions received ad libitum hay and water and were fed a grain concentrate once daily at 0700. In Exp. 1, stallions received either a single injection of dexamethasone (125 microg/kg BW i.m.; n = 5) or vehicle (controls; n = 5) at 0700 on d -1. Starting 24 h later, blood samples were collected every 2 h for 36 h via jugular venipuncture. Cortisol in control stallions varied (P < 0.01) with time, with a morning peak and evening nadir; dexamethasone suppressed (P < 0.01) cortisol concentrations. Leptin and insulin were greater (P < 0.01) in the treated stallions, as was the insulin response to feeding (P < 0.01). Leptin in control stallions varied (P < 0.01) in a diurnal pattern, peaking approximately 10 h after onset of eating. This pattern of leptin secretion was similar, although of greater magnitude (P < 0.01), in treated stallions. In Exp. 2, five stallions were fed the concentrate portion of their diet daily at 0700 and five were switched to feeding at 1900. After 14 d on these regimens, blood samples were collected every 4 h for 48 h and then twice daily for 5 d. Cortisol varied diurnally (P = 0.02) and was not altered (P = 0.21) by feeding time. Insulin and leptin increased (P < 0.01) after feeding, and the peaks in insulin and leptin were shifted 12 h by feeding at 1900. In Exp. 3, six stallions were used in two 3 x 3 Latin square experiments. Treatments were 1) normal daily meal at 0700; 2) no feed for 24 h; and 3) no feed and a bolus injection of insulin (0.4 mIU/kg BW i.v.) followed by infusion of insulin (1.2 mIU.kg BW(-1).min(-1)) for 180 min, which was gradually decreased to 0 by 240 min; sufficient glucose was infused to maintain euglycemia. Plasma insulin increased (P < 0.01) in stallions when they were meal-fed (to approximately 150 microIU/mL) or infused with insulin and glucose (to

  7. Continuous versus Intermittent Infusions of Ceftazidime for Treating Exacerbation of Cystic Fibrosis▿

    PubMed Central

    Hubert, Dominique; Le Roux, Evelyne; Lavrut, Thibaud; Wallaert, Benoit; Scheid, Philippe; Manach, Dominique; Grenet, Dominique; Sermet-Gaudelus, Isabelle; Ramel, Sophie; Cracowski, Claire; Sardet, Anne; Wizla, Nathalie; Deneuville, Eric; Garraffo, Rodolphe

    2009-01-01

    The present multicenter, randomized crossover study compared the safety and efficacy of continuous infusion with those of short infusions of ceftazidime in patients with cystic fibrosis. Patients with chronic Pseudomonas aeruginosa colonization received two successive courses of intravenous tobramycin and ceftazidime (200 mg/kg of body weight/day) for pulmonary exacerbation administered as thrice-daily short infusions or as a continuous infusion. The primary endpoint was the variation in the forced expiratory volume in 1 s (FEV1) during the course of antibiotic treatment. Sixty-nine of the 70 patients enrolled in the study received at least one course of antibiotic treatment. The improvement in FEV1 at the end of therapy was not statistically different between the two treatment procedures (+7.6% after continuous infusion and +5.5% after short infusions) but was better after continuous ceftazidime treatment in patients harboring resistant isolates (P < 0.05). The interval between the course of antibiotic treatments was longer after the continuous infusion than after the short infusion of ceftazidime (P = 0.04). The mean serum ceftazidime concentration during the continuous infusion was 56.2 ± 23.2 μg/ml; the mean peak and trough concentrations during the short infusions were 216.3 ± 71.5 and 12.1 ± 8.7 μg/ml, respectively. The susceptibility profiles of the P. aeruginosa isolates remained unchanged and were similar for both regimens. Quality-of-life scores were similar whatever the treatment procedure, but 82% of the patients preferred the continuous-infusion regimen. Adverse events were not significantly different between the two regimens. In conclusion, the continuous infusion of ceftazidime did not increase its toxicity and appeared to be as efficient as short infusions in patients with cystic fibrosis as a whole, but it gave better results in patients harboring resistant isolates of P. aeruginosa. PMID:19528265

  8. Variable Patterns of Continuous Morphine Infusions at End of Life

    PubMed Central

    Lin, Katrina J.; Ching, Andrea; Edmonds, Kyle P.; Roeland, Eric J.; Revta, Carolyn; Ma, Joseph D.

    2015-01-01

    Abstract Background: Continuous morphine infusions (CMIs) treat pain and dyspnea at the end of life (EOL). CMIs may be initiated at an empiric rate and/or are rapidly escalated without proper titration. Objective: The study objective was to evaluate CMI patterns at the EOL. Methods: This single-center, retrospective chart review evaluated adult patients who died while receiving CMI at EOL. Patient demographics and opioid dosing information were extracted from an electronic medical record. Twenty-four hour IV morphine equivalent was calculated prior to CMI initiation and at the time of death. Results: Of the 190 patient charts, 63.2% (n=120) received no bolus doses prior to CMI initiation. Mean 24-hour IV morphine equivalent prior to CMI initiation was 49.3 mg (range: 0–1200 mg, SD 384.9) and at time of death was 267.1 mg (12.0–5193.2 mg, SD 442.2), representing an increase of +442%. Mean CMI starting rate was 3.3 mg/hour (0.4–30.0 mg/hour, SD 3.6) with titration at time of death to a mean of 7.7 mg/hour (0.4–70.0 mg/hour, SD 9.4), representing an increase of +130%. Mean number of CMI rate adjustments was 2.5 (0–5, SD 3.3); and number of bolus doses administered between titrations was 4.2 (0–27, SD 4.8). Mean time from CMI initiation to death was 15.5 hours (0.05–126.9 hours, SD 21.7). There was a negative association between rate of infusion increase per hour and total number of hours on CMI (r=−0.2, p=0.0062). Conclusions: Hospitalized patients at EOL had a much higher 24-hour IV morphine equivalents and CMI rates at time of death compared to CMI initiation. Variability was observed in the number of CMI rate adjustments and the number of bolus doses administered. PMID:26107143

  9. Continuous infusion of beta-lactam antibiotics in severe infections: a review of its role.

    PubMed

    Roberts, Jason A; Paratz, Jennifer; Paratz, Elizabeth; Krueger, Wolfgang A; Lipman, Jeffrey

    2007-07-01

    Continuous infusion of beta-lactam antibiotics has been widely promoted to optimise their time-dependent activity. Increasing evidence is emerging suggesting potential benefits in patient populations with altered pathophysiology, such as seriously ill patients. From a pharmacokinetic viewpoint, much information supports higher trough concentrations of beta-lactam antibiotics when administered by continuous infusion. This advantage of continuous infusion translates into a superior ability to achieve pharmacodynamic targets, particularly when the minimum inhibitory concentration (MIC) of the pathogen is >or=4 mg/L. One drawback of continuous infusion may be limited physicochemical stability. This issue exists particularly for carbapenem antibiotics whereby prolonged infusions (i.e. >3h) can be used to improve the time above the MIC compared with conventional bolus dosing. Few studies have examined clinical outcomes of bolus and continuous dosing of beta-lactam antibiotics in seriously ill patients. No statistically significant differences have been shown for: mortality; time to normalisation of leukocytosis or pyrexia; or duration of mechanical ventilation, intensive care unit stay or hospital stay. Some evidence suggests improved clinical cure and resolution of illness with continuous infusion in seriously ill patients. Pharmacoeconomic advantages of continuous infusion of beta-lactam antibiotics are well characterised. Available data suggest that seriously ill patients with severe infections requiring significant antibiotic courses (>or=4 days) may be the subgroup that will achieve better outcomes with continuous infusion.

  10. Serum concentrations of amoxicillin in neonates during continuous intravenous infusion.

    PubMed

    van Boekholt, A; Fleuren, H; Mouton, J; Kramers, C; Sprong, T; Gerrits, P; Semmekrot, B

    2016-06-01

    Amoxicillin is commonly used for the treatment of neonatal bacterial infection with intermittent dosing (ID) regimens. However, increasing bacterial resistance, in addition to a lack of new antimicrobial agents, urges the optimization of current therapeutic options. Clinical studies in adults suggest continuous infusion (CI) regimens of beta-lactam antibiotics to be superior to ID. There are as yet no guidelines concerning the CI dosing of amoxicillin. The present study was developed to describe the CI pharmacokinetics and -dynamics of amoxicillin during the first 3 days of life in search of the optimal dosing regimen. Neonates with a gestational age above 34 weeks, at risk of neonatal infection and requiring amoxicillin therapy, were included. Serum concentrations of amoxicillin were measured during CI on days 1 and 3 in the steady state. Twenty-two serum samples of 11 patients were collected. All patients reached and retained serum concentrations of amoxicillin within the therapeutic range without exceeding the toxic concentration (serum concentrations on day 1 mean 55.4 mg/l, range 30.9-69.5, SD 10.5, and on day 3 48.8 mg/l, range 25.5-92.4, SD 18.4). There was no significant decrease in concentration from day 1 to day 3 (p = 0.38). This study showed therapeutic, nontoxic concentrations of amoxicillin in neonates on CI of amoxicillin in the first 3 days of life. Randomized controlled trials should reveal whether the clinical benefits of the CI of amoxicillin exceed those of ID regimens.

  11. No improvement of pancreas transplant endocrine function by exogenous insulin infusion (islet rest) in the postoperative period.

    PubMed

    Dafoe, D C; Campbell, D A; Rosenberg, L; Merion, R M; Ucros, I; Vinik, A I; Klandorf, H; Turcotte, J G

    1989-07-01

    The concept of islet exhaustion maintains that exposure of pancreatic islets to hyperglycemia and other stresses leads to islet dysfunction and irreparable damage. The process of pancreatic transplantation places many stresses on islets (e.g., counter-regulatory hormones, steroids, cyclosporine toxicity). As practiced by some centers, it may be important to administer exogenous insulin in the postoperative period to provide islet rest. Using a porcine pancreas transplant model that simulates clinical transplantation, we studied 2 groups: 1 group (n = 8) received constant insulin infusion for 7 days after transplantation; the control group (n = 5) received vehicle only. The islets in the insulin infusion group were rested as evidenced by a significantly decreased mean C-peptide level (0.27 +/- 0.04 ng/ml) as compared to the control group (0.66 +/- 0.08 ng/ml) (P less than 0.05). After insulin infusion was discontinued, intravenous glucose tolerance testing found insulin, C-peptide and glucagon responses were not different between groups. Glucose clearance was also comparable; K values were -1.79 and -1.60 in the insulin infusion and control groups, respectively. In conclusion, islet rest by insulin infusion for 7 postoperative days did not improve subsequent pancreas transplant endocrine function.

  12. Prospective randomised study of intensive insulin treatment on long term survival after acute myocardial infarction in patients with diabetes mellitus. DIGAMI (Diabetes Mellitus, Insulin Glucose Infusion in Acute Myocardial Infarction) Study Group.

    PubMed Central

    Malmberg, K.

    1997-01-01

    OBJECTIVES: To test the hypothesis that intensive metabolic treatment with insulin-glucose infusion followed by multidose insulin treatment in patients with diabetes mellitus and acute myocardial infarction improves the prognosis. DESIGN: Patients with diabetes mellitus and acute myocardial infarction were randomly allocated standard treatment plus insulin-glucose infusion for at least 24 hours followed by multidose insulin treatment or standard treatment (controls). SUBJECTS: 620 patients were recruited, of whom 306 received intensive insulin treatment and 314 served as controls. MAIN OUTCOME MEASURE: Long term all cause mortality. RESULTS: The mean (range) follow up was 3.4 (1.6-5.6) years. There were 102 (33%) deaths in the treatment group compared with 138 (44%) deaths in the control group (relative risk (95% confidence interval) 0.72 (0.55 to 0.92); P = 0.011). The effect was most pronounced among the predefined group that included 272 patients without previous insulin treatment and at a low cardiovascular risk (0.49 (0.30 to 0.80); P = 0.004). CONCLUSION: Insulin-glucose infusion followed by intensive subcutaneous insulin in diabetic patients with acute myocardial infarction improves long term survival, and the effect seen at one year continues for at least 3.5 years, with an absolute reduction in mortality of 11%. This means that one life was saved for nine treated patients. The effect was most apparent in patients who had not previously received insulin treatment and who were at a low cardiovascular risk. PMID:9169397

  13. Continuous infusion of vancomycin in septic patients receiving continuous renal replacement therapy.

    PubMed

    Covajes, Cecilia; Scolletta, Sabino; Penaccini, Laura; Ocampos-Martinez, Eva; Abdelhadii, Ali; Beumier, Marjorie; Jacobs, Frédérique; de Backer, Daniel; Vincent, Jean-Louis; Taccone, Fabio Silvio

    2013-03-01

    Vancomycin is frequently administered as a continuous infusion to treat severe infections caused by Gram-positive bacteria. Previous studies have suggested a loading dose of 15 mg/kg followed by continuous infusion of 30 mg/kg in patients with normal renal function; however, there are no dosing recommendations in patients with renal failure undergoing continuous renal replacement therapy (CRRT). Data from all adult septic patients admitted to a Department of Intensive Care over a 3-year period in whom vancomycin was given as a continuous infusion were reviewed. Patients were included if they received vancomycin for ≥48h during CRRT. Vancomycin levels were obtained daily. During the study period, 85 patients (56 male; mean age 65±15 years; weight 85±24kg) met the inclusion criteria. Median (interquartile range) APACHE II and SOFA scores were 24 (20-29) and 11 (7-14), respectively, and the overall mortality rate was 59%. Mean vancomycin doses were 16.4±6.4 (loading dose), 23.5±8.1 (Day 1), 23.2±7.4 (Day 2) and 23.3±11.0 (Day 3) mg/kg, resulting in blood concentrations of 24.7±9.0 (Day 1), 26.0±8.1 (Day 2) and 27.7±9.3 (Day 3) μg/mL. On Day 1, 43 patients (51%) had adequate drug concentrations (20-30 μg/mL), 17 (20%) had levels >30 μg/mL and 25 (29%) had levels <20 μg/mL. Most patients with adequate drug concentrations received a daily dose of 16-35 mg/kg. The intensity of CRRT directly influenced vancomycin concentrations on Day 1 of therapy. Copyright © 2012 Elsevier B.V. and the International Society of Chemotherapy. All rights reserved.

  14. Continuous intravenous perioperative lidocaine infusion for postoperative pain and recovery.

    PubMed

    Kranke, Peter; Jokinen, Johanna; Pace, Nathan Leon; Schnabel, Alexander; Hollmann, Markus W; Hahnenkamp, Klaus; Eberhart, Leopold H J; Poepping, Daniel M; Weibel, Stephanie

    2015-07-16

    The management of postoperative pain and recovery is still unsatisfactory in clinical practice. Opioids used for postoperative analgesia are frequently associated with adverse effects including nausea and constipation. These adverse effects prevent smooth postoperative recovery. On the other hand not all patients may be suited to, and take benefit from, epidural analgesia used to enhance postoperative recovery. The non-opioid lidocaine was investigated in several studies for its use in multi-modal management strategies to reduce postoperative pain and enhance recovery. The aim of this review was to assess the effects (benefits and risks) of perioperative intravenous lidocaine infusion compared to placebo/no treatment or compared to epidural analgesia on postoperative pain and recovery in adults undergoing various surgical procedures. We searched the Cochrane Central Register of Controlled Trials (CENTRAL, Issue 5 2014), MEDLINE (January 1966 to May 2014), EMBASE (1980 to May 2014), CINAHL (1982 to May 2014), and reference lists of articles. We searched the trial registry database ClinicalTrials.gov, contacted researchers in the field, and handsearched journals and congress proceedings. We did not apply any language restrictions. We included randomized controlled trials comparing the effect of continuous perioperative intravenous lidocaine infusion either with placebo, or no treatment, or with epidural analgesia in adults undergoing elective or urgent surgery under general anaesthesia. The intravenous lidocaine infusion must have been started intraoperatively prior to incision and continued at least until the end of surgery. Trial quality was independently assessed by two authors according to the methodological procedures specified by the Cochrane Collaboration. Data were extracted by two independent authors. We collected trial data on postoperative pain, recovery of gastrointestinal function, length of hospital stay, postoperative nausea and vomiting (PONV), opioid

  15. Continuous infusion of low-dose doxorubicin, epirubicin and mitoxantrone in cancer chemotherapy: a review.

    PubMed

    Greidanus, J; Willemse, P H; Uges, D R; Oremus, E T; De Langen, Z J; De Vries, E G

    1988-12-09

    With the recent development of reliable portable pumps and safe venous access systems, continuous infusion of chemotherapeutic agents on an out-patient basis has become feasible. Advantages of continuous infusion are the long-term exposure of tumour cells to the drug and the fact that most toxic effects are reduced for doxorubicin, epirubicin and mitoxantrone due to elimination of the high peak plasma levels. Preliminary data for doxorubicin suggest that its antitumour activity is maintained. Pharmacokinetic studies with epirubicin and mitoxantrone showed a linear relationship between drug dose infused and the steady-state plasma level for these drugs. The area under the curve for leukocytes drug level was higher during continuous infusion than after an equitoxic bolus injection of epirubicin and mitoxantrone. Well-randomized clinical trials will be necessary to investigate the role of continuous infusion of antracyclines and mitoxantrone in cancer chemotherapy in the future.

  16. Tolerance to cocaine in brain stimulation reward following continuous cocaine infusions.

    PubMed

    Pudiak, Cindy M; KuoLee, Rhonda; Bozarth, Michael A

    2014-07-01

    This study examined tolerance to cocaine's threshold-lowering effect in brain stimulation reward (BSR) following continuous cocaine infusions and secondly, used the nitric oxide synthase inhibitor Nω-nitro-L-arginine methyl ester (L-NAME) to determine NO's involvement in the development of cocaine tolerance. Animals were continuously infused with saline or cocaine (30 mg/kg per day) via osmotic minipump for 14 days and injected daily with saline or L-NAME (30 mg/kg, i.p.) following BSR testing. Saline-treated animals continuously infused with saline showed stable BSR thresholds across the 14-day infusion period. Saline-treated animals continuously infused with cocaine showed markedly lowered BSR thresholds on Day 1 followed by a progressive increase in BSR thresholds across the infusion period - indicating the development of tolerance. L-NAME-treated animals continuously infused with cocaine showed stimulation thresholds that were not significantly different from saline-treated animals continuously infused with cocaine. A cocaine challenge injection (10 mg/kg, i.p.) administered 3 and again at 10 days following minipump removal revealed that saline-treated animals continuously infused with saline showed lowered BSR thresholds. Saline-treated animals continuously infused with cocaine displayed lowered BSR thresholds that were not significantly different from saline-infused animals. L-NAME treated animals continuously infused with cocaine showed higher BSR thresholds to a challenge 3 days following pump removal. However, stimulation thresholds for this group failed to reach statistical significance on both days (i.e., Days 3 and 10) following pump removal. Results showed that animals continuously infused with cocaine develop robust tolerance to cocaine's threshold-lowering effect during the 14-day infusion period. Tolerance to cocaine's threshold-lowering effect was short-lived and dissipated soon after minipump removal. L-NAME treatment failed to significantly

  17. Effects of intraruminal infusion of propionate on the concentrations of ammonia and insulin in peripheral blood of cows receiving an intraruminal infusion of urea.

    PubMed

    Choung, J J; Chamberlain, D G

    1995-11-01

    To test the hypothesis that propionate can reduce hepatic capacity to detoxify ammonia, effects of the inclusion of propionate in intraruminal infusions of urea on the concentrations of ammonia, other metabolites and insulin in peripheral blood were investigated in two experiments with non-lactating dairy cows. Both experiments were of a 4 x 4 Latin square design with four animals, four treatments and four experimental periods of 7 d; feed was given in two equal meals each day, all intraruminal infusions were given for 1 h at the time of the morning feed, and propionic acid was partly neutralized with NaOH. In Expt 1, the treatments were a basal diet of pelleted lucerne and chopped hay alone or with the following infusions (g/d): urea 80, propionic acid 350, urea 80 plus propionic acid 350. The inclusion of propionate in the urea infusion markedly increased (P < 0.001) the concentration of ammonia in plasma compared with infusion of urea alone. Moreover, the inclusion of urea with the propionate infusion abolished (P < 0.01) the increase in blood insulin level seen with the infusion of propionate alone. In Expt 2, less severe treatments were imposed, the aim being to reproduce metabolic loads of propionate and ammonia that might be expected from a diet of high-protein grass silage rich in lactic acid. The treatments were a basal diet of grass silage alone or with the following infusions (g/d): NaCl 145, NaCl 145 plus urea 50, propionic acid 200, urea 50 plus propionic acid 200. Effects were less pronounced than in Expt 1 but, in the period immediately after infusion, similar effects were seen. It is concluded that propionate-ammonia interactions may have potentially important effects on milk production especially for diets with high proportions of grass silage containing high levels of protein and lactic acid.

  18. Tumour necrosis factor-alpha infusion produced insulin resistance but no change in the incretin effect in healthy volunteers.

    PubMed

    Nielsen, Signe Tellerup; Lehrskov-Schmidt, Louise; Krogh-Madsen, Rikke; Solomon, Thomas P J; Lehrskov-Schmidt, Lars; Holst, Jens Juul; Møller, Kirsten

    2013-11-01

    Type 2 diabetes mellitus (T2DM) is associated with peripheral insulin resistance, impaired incretin effect, and increased plasma levels of tumour necrosis factor-alpha (TNF-α). Although TNF-α infusion at a dose that induces systemic inflammation in healthy volunteers has been demonstrated to induce peripheral insulin resistance, the influence of this cytokine on the incretin effect is unknown. We investigated whether systemic inflammation induced by TNF-α infusion in healthy volunteers alters the incretin hormone response to oral and intravenous glucose loads in a crossover study design with ten healthy male volunteers (mean age 24 years, mean body mass index 23.7 kg/m(2) ). The study consisted of four study days: days 1 and 2, 6-h infusion of saline; days 3 and 4, 6-h infusion of TNF-α; days 1 and 3, 4-h oral glucose tolerance test; and days 2 and 4, 4-h corresponding intravenous isoglycaemic glucose tolerance test. Glucose tolerance tests were initiated after 2 h of saline/TNF-α infusion. Plasma concentrations of TNF-α, interleukin 6, glucose, incretin hormones, and cortisol, and serum concentrations of C-peptide and insulin were measured throughout the study days. Insulin sensitivity was estimated by the Matsuda index and homeostasis model assessment of insulin resistance (HOMA-IR). Prehepatic insulin secretion rates were calculated. TNF-α infusion induced symptoms of systemic inflammation; increased plasma levels of cortisol, TNF-α, and interleukin 6; and increased the HOMA-IR. The secretion of incretin hormones as well as the incretin effect remained unchanged. In healthy young male volunteers, acute systemic inflammation induced by infusion of TNF-α is associated with insulin resistance with no change in the incretin effect. Copyright © 2013 John Wiley & Sons, Ltd.

  19. Glycemic control in cardiac surgery: implementing an evidence-based insulin infusion protocol.

    PubMed

    Hargraves, Joelle D

    2014-05-01

    Acute hyperglycemia following cardiac surgery increases the risk of deep sternal wound infection, significant early morbidity, and mortality. Insulin infusion protocols that target tight glycemic control to treat hyperglycemia have been linked to hypoglycemia and increased mortality. Recently published studies examining glycemic control in critical illness and clinical practice guidelines from professional organizations support moderate glycemic control. To measure critical care nurses' knowledge of glycemic control in cardiac surgery before and after education. To evaluate the safety and effectiveness of an evidence-based insulin infusion protocol targeting moderate glycemic control in cardiac surgery patients. This evidence-based practice change was implemented in the cardiovascular unit in a community teaching hospital. Nurses completed a self-developed questionnaire to measure knowledge of glycemic control. Blood glucose data, collected (retrospectively) from anesthesia end time through 11:59 PM on postoperative day 2, were compared from 2 months before to 2 months after the practice change. Nurses' knowledge (test scores) increased significantly after education (pretest mean = 53.10, SD = 11.75; posttest mean = 79.10, SD = 12.02; t54 = -8.18, P < .001). Mean blood glucose level after implementation was 148 mg/dL. The incidence of hypoglycemia, 2.09% before and 0.22% after the intervention, was significantly reduced ( $${\\hbox{ \\chi }}_{1}^{2}$$ [n = 29] = 13.9, P < .001). The percentage of blood glucose levels less than 180 mg/dL was 88.30%. Increasing nurses' knowledge of glycemic control and implementing an insulin infusion protocol targeting moderate glycemic control were effective for treating acute hyperglycemia following cardiac surgery with decreased incidence of hypoglycemia.

  20. Continuous infusion of piperacillin/tazobactam in patients with severe infections: A possible pharmacokinetic optimisation?

    PubMed

    Attivi, D; Gibaud, S

    2014-05-01

    Piperacillin/Tazobactam is a time-dependent antimicrobial combination (beta-lactam/beta-lactamase inhibitor) commonly used in the treatment of severe Gram-negative infections. The optimisation of its time-dependent bactericidal activity via continuous infusion could improve clinical outcomes. Several studies have been realized on the relevance of a continuous infusion, but, to date, no definitive position can be adopted on the matter and a well-designed randomized controlled trial is warranted. In other articles, continuous infusion regimens are also more cost efficient. This article is an update, including the most recent trials about this subject.

  1. Pharmacokinetics and Clinical Utility of Valproic Acid Administered via Continuous Infusion.

    PubMed

    Cook, Aaron M; Zafar, Muhammad S; Mathias, Sally; Stewart, Alejandra M; Albuja, Ana C; Bensalem-Owen, Meriem; Kapoor, Siddharth; Baumann, Robert J

    2016-01-01

    Valproic acid is a versatile antiepileptic drug that is often used in the acute care setting. Intravenous valproic acid lends itself well to a continuous infusion as it exhibits a relatively short half-life. We evaluated the pharmacokinetics and clinical efficacy of continuous infusion valproic acid in hospitalized patients with migraine and seizures. A retrospective cohort study was performed utilizing information from the medical records of patients receiving an intravenous continuous infusion of valproic acid. Patients were included if they were aged 1 month to 85 years and they received a continuous infusion of valproic acid. Therapeutic response, common adverse effects, and the pharmacokinetic profile of valproic acid were evaluated. Continuous infusion valproic acid led to a concentration within the desired range (50-100 μg/ml) in 83.4% of patients, a rate that was higher in pediatric patients. The clinical response rate was also higher in pediatric patients with seizures or migraines and appeared to be better when the concentration was >75 μg/ml. Analysis of safety parameters suggests similar safety considerations to valproic acid when administered via intermittent infusion. Continuous infusion valproic acid appears to be a safe, effective, and predictable manner by which to administer valproic acid to pediatric and adult patients admitted to the hospital.

  2. Use of continuous infusion pumps during radiation treatment.

    PubMed

    Bak, Kate; Gutierrez, Eric; Lockhart, Elizabeth; Sharpe, Michael; Green, Esther; Costa, Sarah; Hertz, Sherrie; Kaizer, Leonard; Whitton, Anthtony; Warde, Padraig

    2013-03-01

    Despite increasing chemoradiotherapy treatment, there is a paucity of information regarding the effects of radiation exposure on ambulatory infusion pumps used to deliver chemotherapy or other essential medications. The aim of this overview is to present the available evidence on this subject, heighten awareness within the clinical community, provide considerations for minimizing possible negative effects on patient care, and encourage the monitoring of infusion devices after exposure to radiation or electromagnetic interference. Published literature was systematically searched using MEDLINE and EMBASE; gray literature was searched using Google and an environmental scan of relevant Web sites. A multidisciplinary working group reviewed the compiled evidence, and a draft of the document was sent to health professionals from various disciplines for an external review. Four reports and three manufacturer device alerts were identified that suggest a risk of pump malfunction as a result of radiation exposure. The estimated cumulative dose at which pump failure has been reported ranges from 28.5 to 42 Gy; however, additional clinical investigations should be undertaken. Pump relocation, pump shielding, and assessment of the pump after radiation exposure are most commonly suggested to minimize pump malfunction related to radiation exposure. A list of additional considerations is offered for those developing institution specific policies and procedures based on the available evidence and expert consensus. The varied and unpredictable results of radiation exposure on infusion devices suggest that additional testing should be carried out to determine the limits of dose exposure and to raise awareness around this patient safety issue.

  3. Continuous-Infusion Antipseudomonal Beta-Lactam Therapy in Patients With Cystic Fibrosis

    PubMed Central

    Prescott, William A.; Gentile, Allison E.; Nagel, Jerod L.; Pettit, Rebecca S.

    2011-01-01

    Objective: We sought to evaluate the pharmacokinetics, efficacy, safety, stability, pharmacoeconomics, and quality-of-life effects of continuous-infusion antipseudomonal beta-lactam therapy in patients with cystic fibrosis (CF). Data Sources: Literature retrieval was accessed through Medline (from 1950 to December 2010) using the following terms: cystic fibrosis; beta-lactams or piperacillin or ticarcillin or cefepime or ceftazidime or doripenem or meropenem or imipenem/cilastin or aztreonam; continuous infusion or constant infusion; drug stability; economics, pharmaceutical; and quality of life. In addition, reference citations from identified publications were reviewed. Study Selection and Data Extraction: We evaluated all articles in English identified from the data sources. Data Synthesis: Patients with CF often harbor colonies of multidrug-resistant organisms, increasing the risk of suboptimal dosing and failure to meet the time above the minimum inhibitory concentration (T > MIC) pharmacodynamic targets. The pharmacokinetics of continuous-infusion antipseudomonal beta-lactam therapy in CF maintains serum concentrations above the MIC of susceptible strains and is more likely than intermittent infusion to achieve optimal T > MIC targets for some intermediate and resistant strains of Pseudomonas aeruginosa. Three noncomparative and four comparative studies have assessed the efficacy and safety of continuous-infusion antipseudomonal beta-lactam therapy during CF pulmonary exacerbations. Ceftazidime, the most extensively studied antibiotic for continuous infusion in CF, has been shown to improve forced expiratory volume in 1 second (FEV1), to improve forced vital capacity (FVC), and to extend the time between pulmonary exacerbations. Continuous-infusion cefepime has been studied in a small number of patients, and a trend toward improved pulmonary function has been observed. Continuous-infusion antipseudomonal beta-lactam therapy appears to be well tolerated

  4. Improvement in glycemia after glucose or insulin overload in leptin-infused rats is associated with insulin-related activation of hepatic glucose metabolism.

    PubMed

    Burgos-Ramos, Emma; Canelles, Sandra; Frago, Laura M; Chowen, Julie A; Arilla-Ferreiro, Eduardo; Argente, Jesús; Barrios, Vicente

    2016-01-01

    Insulin regulates glucose homeostasis through direct effects on the liver, among other organs, with leptin modulating insulin's hepatic actions. Since central leptin may modify insulin signaling in the liver, we hypothesized that leptin infusion activates hepatic glycogen synthesis following peripheral administration of a bolus of glucose or insulin, thus regulating glycemia. Oral glucose and intraperitoneal insulin tolerance tests were performed in control, intracerebroventricular leptin-treated and pair-fed rats during 14 days. An improvement in glycemia and an increase in hepatic free glucose and glycogen concentrations after glucose or insulin overload were observed in leptin-treated rats. In order to analyze whether the liver was involved in these changes, we studied activation of insulin signaling by Western blotting and multiplex bead immunoassay after leptin infusion. Our studies revealed an increase in phosphorylation of insulin receptor substrate-1 and Akt in leptin-treated rats. Examination of parameters related to glucose uptake and metabolism in the liver revealed an augment in glucose transporter 2 and a decrease in phosphoenolpyruvate carboxylase protein levels in this group. These results indicate that central leptin increases hepatic insulin signaling, associated with increased glycogen concentrations after glucose or insulin overload, leading to an improvement in glycemia.

  5. Guidelines for the use of an insulin infusion for the management of hyperglycemia in critically ill patients.

    PubMed

    Jacobi, Judith; Bircher, Nicholas; Krinsley, James; Agus, Michael; Braithwaite, Susan S; Deutschman, Clifford; Freire, Amado X; Geehan, Douglas; Kohl, Benjamin; Nasraway, Stanley A; Rigby, Mark; Sands, Karen; Schallom, Lynn; Taylor, Beth; Umpierrez, Guillermo; Mazuski, John; Schunemann, Holger

    2012-12-01

    To evaluate the literature and identify important aspects of insulin therapy that facilitate safe and effective infusion therapy for a defined glycemic end point. Where available, the literature was evaluated using Grades of Recommendation, Assessment, Development, and Evaluation (GRADE) methodology to assess the impact of insulin infusions on outcome for general intensive care unit patients and those in specific subsets of neurologic injury, traumatic injury, and cardiovascular surgery. Elements that contribute to safe and effective insulin infusion therapy were determined through literature review and expert opinion. The majority of the literature supporting the use of insulin infusion therapy for critically ill patients lacks adequate strength to support more than weak recommendations, termed suggestions, such that the difference between desirable and undesirable effect of a given intervention is not always clear. The article is focused on a suggested glycemic control end point such that a blood glucose ≥ 150 mg/dL triggers interventions to maintain blood glucose below that level and absolutely <180 mg/dL. There is a slight reduction in mortality with this treatment end point for general intensive care unit patients and reductions in morbidity for perioperative patients, postoperative cardiac surgery patients, post-traumatic injury patients, and neurologic injury patients. We suggest that the insulin regimen and monitoring system be designed to avoid and detect hypoglycemia (blood glucose ≤ 70 mg/dL) and to minimize glycemic variability.Important processes of care for insulin therapy include use of a reliable insulin infusion protocol, frequent blood glucose monitoring, and avoidance of finger-stick glucose testing through the use of arterial or venous glucose samples. The essential components of an insulin infusion system include use of a validated insulin titration program, availability of appropriate staffing resources, accurate monitoring technology, and

  6. Food image-induced brain activation is not diminished by insulin infusion

    PubMed Central

    Belfort-DeAguiar, Renata; Seo, Dongju; Naik, Sarita; Hwang, Janice; Lacadie, Cheryl; Schmidt, Christian; Constable, R. Todd; Sinha, Rajita; Sherwin, Robert

    2016-01-01

    Background/Objective The obesity epidemic appears to be driven in large part by our modern environment inundated by food cues, which may influence our desire to eat. While insulin decreases food intake in both animals and humans, the effect of insulin on motivation for food in the presence of food cues is not known. Therefore, the aim of this study was to evaluate the effect of an intravenous insulin infusion on the brain response to visual food cues, hunger and food craving in non-obese human subjects. Subjects/Methods Thirty-four right-handed healthy non-obese subjects (19F/15M, age: 29±8 yrs.; BMI: 23.1±2.1 kg/m2) were divided in two groups matched by age, and BMI: the Insulin Group (18 subjects) underwent a hyperinsulinemic-euglycemic-clamp, and the control group (16 subjects) received an intravenous saline infusion, while viewing high and low-calorie food and non-food pictures during a functional MRI scan. Motivation for food was determined via analogue scales for hunger, wanting and liking ratings. Results Food images induced brain responses in the hypothalamus, striatum, amygdala, insula, ventromedial prefrontal cortex (PFC), dorsolateral PFC, and occipital lobe (whole brain correction, P<0.05). Wanting (P<0.001) and liking (P<0.001) ratings were significantly higher for the food than the non-food images, but not different between insulin and saline infusion groups. Hunger ratings increased throughout the MRI scan and correlated with preference for high-calorie food pictures (r=0.70; P<0.001). However neither brain activity nor food craving were affected by hyperinsulinemia or hormonal status (leptin and ghrelin levels) (P=NS). Conclusion Our data demonstrate that visual food cues induce a strong response in motivation/reward and cognitive-executive control brain regions in non-obese subjects, but that these responses are not diminished by hyperinsulinemia per se. These findings suggest that our modern food cue saturated environment may be sufficient to

  7. Bolus versus continuous infusion of microbubble contrast agent for liver US: initial experience.

    PubMed

    Okada, Masahiro; Hoffmann, Christian W; Wolf, Karl J; Albrecht, Thomas

    2005-12-01

    Institutional review board approval and informed consent were obtained. To prospectively assess if continuous infusion of galactose-palmitic acid can prolong the duration of hepatic enhancement at ultrasonography over bolus injection, 11 patients received two injections--one bolus injection (2 mL/sec) and one continuous infusion (1.5 mL/min)--with the same dose of galactose-palmitic acid (4 g, 300 mg/dL). Two unenhanced baseline sweep scans (mechanical index of 0.7 and 1.3) of the relevant liver lobe were acquired followed by contrast-enhanced sweeps after bolus injection and continuous infusion. Each sweep was saved as cine loops and analyzed with a personal computer. Duration of enhancement more than 3 dB was prolonged by continuous infusion from 4.3 minutes +/- 2.4 (+/-standard deviation) at bolus injection to 10.1 minutes +/- 3.0 (P < .005). Maximal parenchymal enhancement was 11.0 dB +/- 3.2 (bolus injection) and 9.2 dB +/- 3.8 (infusion, P < .05). Peak liver-to-lesion contrast was 14.2 dB +/- 6.3 (bolus injection) and 13.2 dB +/- 7.1 (infusion, not significant). Continuous infusion of galactose-palmitic acid markedly prolongs but slightly diminishes hepatic enhancement; liver-to-lesion contrast remains unchanged.

  8. Therapeutic Drug Monitoring of Continuous Infusion Doripenem in a Pediatric Patient on Continuous Renal Replacement Therapy

    PubMed Central

    Moore, Wayne S.; Conley, Susan B.; Shea, Paul; Enache, Adela; Chopra, Arun

    2017-01-01

    An 11-year-old African American male with severe combined immunodeficiency variant, non-cystic fibrosis bronchiectasis, pancreatic insufficiency, chronic mycobacterium avium-intracellulare infection, chronic sinusitis, and malnutrition presented with a 1-week history of fevers. He subsequently developed respiratory decompensation and cefepime was discontinued and doripenem was initiated. Doripenem was the carbapenem used due to a national shortage of meropenem. By day 7 the patient (24.7 kg) had a positive fluid balance of 6925 mL (28% FO), and on days 7 into 8 developed acute kidney injury evidenced by an elevated serum creatinine of 0.68 mg/dL, an increase from the baseline of 0.28 mg/dL. On day 9, the patient was initiated on continuous renal replacement therapy (CRRT) and the doripenem dosing was changed to a continuous infusion of 2.5 mg/kg/hr (60 mg/kg/day). Approximately 12.5 hours after the start of the doripenem a serum concentration was obtained, which was 4.01 mg/L corresponding to a clearance of 10.5 mL/min/kg. The pediatric dosing and pharmacokinetic data available for doripenem suggest a clearance estimate of 4.4 to 4.8 mL/min/kg, and the adult clearance estimate is 2.4 to 3.78 mL/min/kg. The calculated clearance in our patient of 10.5 mL/min/kg is over double the highest clearance estimate in the pediatric literature. This case demonstrates that doripenem clearance is significantly increased with CRRT in comparison with the published pediatric and adult data. An appropriate pharmacodynamic outcome (time that free drug concentration > minimum inhibitory concentration) can be achieved by continuous infusion doripenem with concurrent therapeutic drug monitoring.

  9. Therapeutic Drug Monitoring of Continuous Infusion Doripenem in a Pediatric Patient on Continuous Renal Replacement Therapy.

    PubMed

    Cies, Jeffrey J; Moore, Wayne S; Conley, Susan B; Shea, Paul; Enache, Adela; Chopra, Arun

    2017-01-01

    An 11-year-old African American male with severe combined immunodeficiency variant, non-cystic fibrosis bronchiectasis, pancreatic insufficiency, chronic mycobacterium avium-intracellulare infection, chronic sinusitis, and malnutrition presented with a 1-week history of fevers. He subsequently developed respiratory decompensation and cefepime was discontinued and doripenem was initiated. Doripenem was the carbapenem used due to a national shortage of meropenem. By day 7 the patient (24.7 kg) had a positive fluid balance of 6925 mL (28% FO), and on days 7 into 8 developed acute kidney injury evidenced by an elevated serum creatinine of 0.68 mg/dL, an increase from the baseline of 0.28 mg/dL. On day 9, the patient was initiated on continuous renal replacement therapy (CRRT) and the doripenem dosing was changed to a continuous infusion of 2.5 mg/kg/hr (60 mg/kg/day). Approximately 12.5 hours after the start of the doripenem a serum concentration was obtained, which was 4.01 mg/L corresponding to a clearance of 10.5 mL/min/kg. The pediatric dosing and pharmacokinetic data available for doripenem suggest a clearance estimate of 4.4 to 4.8 mL/min/kg, and the adult clearance estimate is 2.4 to 3.78 mL/min/kg. The calculated clearance in our patient of 10.5 mL/min/kg is over double the highest clearance estimate in the pediatric literature. This case demonstrates that doripenem clearance is significantly increased with CRRT in comparison with the published pediatric and adult data. An appropriate pharmacodynamic outcome (time that free drug concentration > minimum inhibitory concentration) can be achieved by continuous infusion doripenem with concurrent therapeutic drug monitoring.

  10. Use of Continuous Infusion Pumps During Radiation Treatment

    PubMed Central

    Bak, Kate; Gutierrez, Eric; Lockhart, Elizabeth; Sharpe, Michael; Green, Esther; Costa, Sarah; Hertz, Sherrie; Kaizer, Leonard; Whitton, Anthtony; Warde, Padraig

    2013-01-01

    Introduction: Despite increasing chemoradiotherapy treatment, there is a paucity of information regarding the effects of radiation exposure on ambulatory infusion pumps used to deliver chemotherapy or other essential medications. The aim of this overview is to present the available evidence on this subject, heighten awareness within the clinical community, provide considerations for minimizing possible negative effects on patient care, and encourage the monitoring of infusion devices after exposure to radiation or electromagnetic interference. Methods: Published literature was systematically searched using MEDLINE and EMBASE; gray literature was searched using Google and an environmental scan of relevant Web sites. A multidisciplinary working group reviewed the compiled evidence, and a draft of the document was sent to health professionals from various disciplines for an external review. Results: Four reports and three manufacturer device alerts were identified that suggest a risk of pump malfunction as a result of radiation exposure. The estimated cumulative dose at which pump failure has been reported ranges from 28.5 to 42 Gy; however, additional clinical investigations should be undertaken. Pump relocation, pump shielding, and assessment of the pump after radiation exposure are most commonly suggested to minimize pump malfunction related to radiation exposure. A list of additional considerations is offered for those developing institution specific policies and procedures based on the available evidence and expert consensus. Conclusion: The varied and unpredictable results of radiation exposure on infusion devices suggest that additional testing should be carried out to determine the limits of dose exposure and to raise awareness around this patient safety issue. PMID:23814520

  11. Use of a two-stage insulin infusion study to assess the relationship between insulin suppression of lipolysis and insulin-mediated glucose uptake in overweight/obese, nondiabetic women.

    PubMed

    McLaughlin, Tracey; Yee, Gail; Glassford, Alec; Lamendola, Cindy; Reaven, Gerald

    2011-12-01

    Differences in insulin regulation of free fatty acids (FFAs) are not readily apparent at the same insulin concentrations used to differentiate relative insulin-mediated glucose disposal. Resistance to insulin-mediated glucose disposal and higher daylong FFA concentrations occur more commonly in obese individuals. However, the relationship between the ability of insulin to suppress FFA release from adipose tissue and stimulate glucose disposal in muscle has not been clearly defined in this population. The current study was initiated to test the hypothesis that these 2 facets of insulin action are related, with greater defects in insulin-mediated glucose disposal associated with less effective insulin inhibition of FFA release from adipose tissue. Subjects included 56 healthy nondiabetic overweight/moderately obese women classified as insulin resistant or insulin sensitive based on whole-body glucose disposal. All underwent a modified 240-minute 2-stage insulin infusion with basal (∼15 µU/mL) and physiologically elevated (∼80 µU/mL) steady-state insulin concentrations. Plasma glucose, insulin, FFA, and glycerol were measured throughout. Whereas plasma glucose differed most during physiological hyperinsulinemia in insulin-resistant vs insulin-sensitive subjects, plasma FFA/glycerol differed most during basal insulin concentrations. The FFA concentrations during the basal insulin steady state correlated highly (r = 0.85, P < .001) with glucose concentrations during the hyperinsulinemic steady state. Overweight/moderately obese women exhibit dramatic differences in the ability of insulin to suppress plasma FFA, which correlate highly with differences in insulin-mediated glucose disposal. Variability in insulin regulation of FFA is most apparent at basal insulin concentrations, whereas differences in glucose disposal are most apparent during physiologic hyperinsulinemia. Both can be quantified using a simple 2-stage insulin infusion study, with first-stage FFA

  12. Chronic central leptin infusion modulates the glycemia response to insulin administration in male rats through regulation of hepatic glucose metabolism.

    PubMed

    Burgos-Ramos, Emma; Canelles, Sandra; Rodríguez, Amaia; Gómez-Ambrosi, Javier; Frago, Laura M; Chowen, Julie A; Frühbeck, Gema; Argente, Jesús; Barrios, Vicente

    2015-11-05

    Leptin and insulin use overlapping signaling mechanisms to modify hepatic glucose metabolism, which is critical in maintaining normal glycemia. We examined the effect of an increase in central leptin and insulin on hepatic glucose metabolism and its influence on serum glucose levels. Chronic leptin infusion increased serum leptin and reduced hepatic SH-phosphotyrosine phosphatase 1, the association of suppressor of cytokine signaling 3 to the insulin receptor in liver and the rise in glycemia induced by central insulin. Leptin also decreased hepatic phosphoenolpyruvate carboxykinase levels and increased insulin's ability to phosphorylate insulin receptor substrate-1, Akt and glycogen synthase kinase on Ser9 and to stimulate glucose transporter 2 and glycogen levels. Peripheral leptin treatment reproduced some of these changes, but to a lesser extent. Our data indicate that leptin increases the hepatic response to a rise in insulin, suggesting that pharmacological manipulation of leptin targets may be of interest for controlling glycemia. Copyright © 2015 Elsevier Ireland Ltd. All rights reserved.

  13. Pilot experience with continuous infusion alemtuzumab in patients with fludarabine-refractory chronic lymphocytic leukemia.

    PubMed

    Ferrajoli, Alessandra; Wierda, William G; LaPushin, Ruth; O'Brien, Susan M; Faderl, Stefan; Browning, Mary L; Keating, Michael J

    2008-04-01

    We evaluated the activity and tolerability of alemtuzumab given as a continuous infusion for 7 d followed by subcutaneous administration for 11 wk as salvage therapy for 10 patients with fludarabine-refractory chronic lymphocytic leukemia. The continuous infusion of alemtuzumab was well tolerated. The typical infusion reaction seen with intravenous alemtuzumab was abolished. Two patients achieved a partial response with an overall response rate of 20%. Alemtuzumab levels were measured in four patients and detectable levels were obtained in three. Clinical activity needs to be confirmed in a larger patient population.

  14. Consumption of Ocimum sanctum L. and Citrus paradisi infusions modulates lipid metabolism and insulin resistance in obese rats.

    PubMed

    Gamboa-Gómez, Claudia; Salgado, Luis M; González-Gallardo, Adriana; Ramos-Gómez, Minerva; Loarca-Piña, Guadalupe; Reynoso-Camacho, Rosalía

    2014-05-01

    A high saturated fat and fructose diet leads to metabolic disorders through dysregulation of genes involved in lipid metabolism. Consumption of plant infusions reduces these obesity alterations, but the precise mechanism remains unclear. In this study, we investigated the effect and the possible mechanism of Ocimum sanctum L. (OS) and Citrus paradisi (CP) infusions in diet-induced obese rats. CP and OS infusions suppressed hepatic tissue fat accumulation, and significantly down-regulated the mRNA levels of two hepatic lipogenesis genes: sterol regulatory element binding protein 1c (SREBP1c) and fatty acid synthase (FAS) compared with the obese control. Treatment with these infusions up-regulated the hepatic expression of mRNA related to mitochondrial fatty acid uptake: peroxisome proliferator activated receptor alpha (PPARα) and the expression of carnitine palmitoyl-transferase 1a (CPT1a). Both infusions improved insulin resistance, with OS showing the major effect. Consumption of these infusions reduces the damage caused by free radicals, protecting hepatic lipids and proteins. Additionally, plant infusions increase activity of hepatic enzymes: glutathione S-transferase (GST), glutathione peroxidase (GPX), and catalase (CAT). Our results suggest that the effects of CP and OS infusions on lipid metabolism are related to the down-regulation of genes involved in lipogenesis, particularly for OS, and to the increase in lipid β-oxidation, especially for CP infusion. In conclusion, the consumption of these plant infusions is a feasible adjuvant therapy for metabolic changes induced by obesity.

  15. Integrated insulin pump therapy with continuous glucose monitoring for improved adherence: technology update.

    PubMed

    Tumminia, Andrea; Sciacca, Laura; Frittitta, Lucia; Squatrito, Sebastiano; Vigneri, Riccardo; Le Moli, Rosario; Tomaselli, Letizia

    2015-01-01

    Insulin pump therapy combined with real-time continuous glucose monitoring, known as sensor-augmented pump (SAP) therapy, has been shown to improve metabolic control and to reduce the rate of hypoglycemia in adults with type 1 diabetes compared to multiple daily injections or standard continuous subcutaneous insulin infusion. Glycemic variability is also reduced in patients on SAP therapy. This approach allows patients to monitor their glucose levels being informed of glycemic concentration and trend. Trained diabetic patients, therefore, can appropriately modify insulin infusion and/or carbohydrate intake in order to prevent hypo- or hyperglycemia. For these reasons, SAP therapy is now considered the gold standard for type 1 diabetes treatment. To be clinically effective, however, devices and techniques using advanced technology should not only have the potential to theoretically ameliorate metabolic control, but also be well accepted by patients in terms of satisfaction and health-related quality of life, because these factors will improve treatment adherence and consequently overall outcome. SAP therapy is generally well tolerated by patients; however, many clinical trials have identified significant noncompliance in the use of this device, most notably in the pediatric and adolescent populations. In this review we aim to analyze the main reasons for good or poor adherence to SAP therapy and to provide useful tips in order to fully benefit from this kind of novel therapeutic approach.

  16. Hepatotoxicity After Continuous Amiodarone Infusion in a Postoperative Cardiac Infant

    PubMed Central

    Kicker, Jennifer S.; Haizlip, Julie A.; Buck, Marcia L.

    2012-01-01

    A former 34-week-old female infant with Down syndrome underwent surgical correction of a congenital heart defect at 5 months of age. Her postoperative course was complicated by severe pulmonary hypertension and junctional ectopic tachycardia. Following treatment with amiodarone infusion, she developed laboratory indices of acute liver injury. At their peak, liver transaminase levels were 19 to 35 times greater than the upper limit of normal. Transaminitis was accompanied by coagulopathy, hyperammonemia, and high serum lactate and lipid levels. Hepatic laboratory abnormalities began to resolve within 48 hr of stopping amiodarone infusion. Heart rate control was achieved concurrently with discovery of laboratory test result abnormalities, and no further antiarrhythmic therapy was required. The intravenous formulation of amiodarone contains the diluent polysorbate 80, which may have hepatotoxic effects. Specifically, animal studies suggest that polysorbate 80 may destabilize cell membranes and predispose to fatty change within liver architecture. Polysorbate was implicated in infant fatalities from E-ferol use in the 1980s. This case illustrates a possible adverse event by the Naranjo probability scale. Given the extent of clinically apparent hepatic injury, this patient was not rechallenged with amiodarone during the remainder of her hospitalization. With amiodarone now used as first-line pharmacologic therapy for critical tachyarrhythmia in this population, the number of children exposed to this drug should be expected to increase. Laboratory indices of liver function should be evaluated at initiation of amiodarone therapy, as well as frequently throughout duration of therapy. Consideration should be given to polysorbate-free formulation of intravenous amiodarone for use in the cohort with congenital cardiac disease. PMID:23118673

  17. Closed-loop Continuous Infusions of Etomidate and Etomidate Analogs in Rats

    PubMed Central

    Cotten, Joseph F.; Le Ge, Ri; Banacos, Natalie; Pejo, Ervin; Husain, S. Shaukat; Williams, James H.; Raines, Douglas E.

    2012-01-01

    Background Etomidate is a sedative–hypnotic that is often given as a single intravenous bolus but rarely as an infusion because it suppresses adrenocortical function. Methoxycarbonyl etomidate and (R)-ethyl 1-(1-phenylethyl)-1H-pyrrole-2-carboxylate (carboetomidate) are etomidate analogs that do not produce significant adrenocortical suppression when given as a single bolus. However, the effects of continuous infusions on adrenocortical function are unknown. In this study, we compared the effects of continuous infusions of etomidate, methoxycarbonyl etomidate, and carboetomidate on adrenocortical function in a rat model. Methods A closed-loop system using the electroencephalographic burst suppression ratio as the feedback was used to administer continuous infusions of etomidate, methoxycarbonyl etomidate, or carboetomidate to Sprague–Dawley rats. Adrenocortical function was assessed during and after infusion by repetitively administering adrenocorticotropic hormone 1–24 and measuring serum corticosterone concentrations every 30 min. Results The sedative–hypnotic doses required to maintain a 40% burst suppression ratio in the presence of isoflurane, 1%, and the rate of burst suppression ratio recovery on infusion terminationvaried(methoxycarbonyletomidate>carboetomidate > etomidate). Serum corticosterone concentrations were reduced by 85% and 56% during 30-min infusions of etomidate and methoxycarbonyl etomidate, respectively. On infusion termination, serum corticosterone concentrations recovered within 30 min with methoxycarbonyl etomidate but persisted beyond an hour with etomidate. Carboetomidate had no effect on serum corticosterone concentrations during or after continuous infusion. Conclusions Our results suggest that methoxycarbonyl etomidate and carboetomidate may have clinical utility as sedative–hypnotic maintenance agents when hemodynamic stability is desirable. PMID:21572317

  18. Use of Continuous Infusion Hydralazine in a Pediatric Patient on Mechanical Circulatory Support

    PubMed Central

    Dillman, Nicholas O.; Anders, Marc M.

    2016-01-01

    Hydralazine is a direct peripheral arterial vasodilator used for acute hypertension. Usually administered as a bolus dose, continuous infusion has been described during pregnancy for preeclampsia and eclampsia and in limited reports in cardiac surgeries for afterload reduction. This case describes the use of continuous infusion hydralazine for afterload reduction in an infant receiving extracorporeal membrane oxygenation (ECMO) post–cardiac surgery. Postsurgery, the patient's mean arterial pressures (MAPs) could not be controlled despite escalating doses of vasodilatory medications including nitroprusside, nicardipine, and milrinone; hence, continuous infusion hydralazine was initiated. Although the initiation of a hydralazine infusion produced a decrease in MAP, the response was unsustainable. This case highlights an alternative method for managing systemic vascular resistance and cardiac output to allow for myocardial recovery after cardiac surgery and use of extracorporeal support. At the time of this writing, this is the first published case describing hydralazine administration via continuous infusion in pediatric patients. The use of continuous infusion hydralazine for afterload reduction provided a brief, non-sustained reduction in MAP in a post–cardiac surgery infant managed on ECMO support. PMID:27453704

  19. Low-dose continuous infusion of factor VIII in patients with haemophilia A

    PubMed Central

    Prelog, Tomaž; Dolničar, Majda Benedik; Kitanovski, Lidija

    2016-01-01

    Background Patients with haemophilia A (HA) or B (HB) can be given prophylactic or on-demand treatment administered by continuous infusion or bolus injections of factor VIII (FVIII) or IX (FIX). In this study we evaluated the efficacy and safety of low-dose continuous infusion of FVIII or FIX. Material and methods We studied all eligible patients with HA or HB treated with continuous infusion of factor concentrates over an 18-year period in a single Slovenian Haemophilia Comprehensive Care Centre. Treatment started with a bolus injection of FVIII or FIX, followed by continuous infusion at the initial rate of 2 IU/kg/h of FVIII in HA patients and 4.5 IU/kg/h of FIX in HB patients. The infusion rate was subsequently adjusted according to the indication for therapy. Results A total of 66 continuous infusions (40 in major surgery, 10 in minor surgery and 16 with bleeding episode) in 46 HA patients and 16 (15 in severe and 1 in mild HA) in eight HB patients were included in the study. During the first week of treatment, the median continuous infusion rates in HA patients undergoing major surgery, minor surgery and a bleeding event were 2.18 (0.75–3.68), 1.48 (1.0–2.54) and 2.24 (1.33–3.93) IU/kg/h, respectively. The median FVIII activities were 0.69 (0.37–1.19), 0.47 (0.39–0.84) and 0.52 (0.36–1.06) IU/mL. After the first week of treatment, even lower doses of FVIII were needed. Red blood cell transfusions had to be administered to three patients (2 with severe and 1 with moderate HA) during the continuous infusion and inhibitors developed in five patients. In HB patients, the median continuous infusion rate was 1.85 (1.07–2.94) IU/kg/h and the median FIX activity was 0.62 (0.30–1.04) IU/mL. Red blood cell transfusions were not required, and thrombophlebitis and inhibitors did not appear. Discussion Overall, low-dose continuous infusion was shown to be an effective and safe way of treating patients with HA. The protocol used also proved efficient and

  20. Periodic extraction of interstitial fluid from the site of subcutaneous insulin infusion for the measurement of glucose: a novel single-port technique for the treatment of type 1 diabetes patients.

    PubMed

    Regittnig, Werner; Lindpointner, Stefan; Korsatko, Stefan; Tutkur, Dina; Bodenlenz, Manfred; Pieber, Thomas R

    2013-01-01

    Treatment of type 1 diabetes patients could be simplified if the site of subcutaneous insulin infusion could also be used for the measurement of glucose. This study aimed to assess the agreement between blood glucose concentrations and glucose levels in the interstitial fluid (ISF) that is extracted from the insulin infusion site during periodic short-term interruptions of continuous subcutaneous insulin infusion (CSII). A perforated cannula (24 gauge) was inserted into subcutaneous adipose tissue of C-peptide-negative type 1 diabetes subjects (n=13) and used alternately to infuse rapid-acting insulin (100 U/mL) and to extract ISF glucose during a fasting period and after ingestion of a standard oral glucose load (75 g). Although periodically interrupted for extracting glucose (every hour for approximately 10 min), insulin infusion with the cannula was adequate to achieve euglycemia during fasting and to restore euglycemia after glucose ingestion. Furthermore, the ISF-derived estimates of plasma glucose levels agreed well with plasma glucose concentrations. Correlation coefficient and median absolute relative difference values were found to be 0.95 and 8.0%, respectively. Error grid analysis showed 99.0% of all ISF glucose values within clinically acceptable Zones A and B (83.5% Zone A, 15.5% Zone B). Results show that ISF glucose concentrations measured at the insulin infusion site during periodic short-term interruptions of CSII closely reflect blood glucose levels, thus suggesting that glucose monitoring and insulin delivery may be performed alternately at the same tissue site. A single-port device of this type could be used to simplify and improve glucose management in diabetes.

  1. Acute hypoglycemic, hypocholesterolemic and hypotriglyceridemic effects of continuous intravenous infusion of a lyophilised aqueous extract of Ajuga iva L. Schreber whole plant in streptozotocin-induced diabetic rats.

    PubMed

    El-Hilaly, Jaouad; Tahraoui, Adil; Israili, Zafar H; Lyoussi, Badiâa

    2007-10-01

    The hypoglycemic and hypolipidemic effect of continuous intravenous infusion of a lyophilised aqueous extract of the whole plant Ajuga iva (L.) Schreber (Labiatae) (AI-extract) was investigated in anesthetized normal and streptozotocin (STZ)-induced diabetic rats. The AI-extract was administered to a group of rats by continuous intravenous infusion for 4 h at a dose of 4.2 microg/min/100 g body weight; another group was infused with taurine, the reference compound, at the same dose. In normal rats, AI-extract infusion had no effect on plasma glucose or triglycerides, but plasma cholesterol levels were significantly decreased (22%; P<0.05). However, taurine infusion produced significant hypoglycemic, hypocholesterolemic and hypotriglyceridemic effects (all changes, P<0.05). In STZ-diabetic rats, AI-extract infusion reduced plasma levels of glucose by 24 % (P<0.05), cholesterol by 35% (P<0.01) and triglycerides by 13% (P<0.05). Infusion with taurine produced a greater fall in plasma glucose (72%, P<0.01), cholesterol (54%; P<0.001) and triglyceride (24%; P<0.001) levels. Our results indicate that intravenously administered AI-extract exerts hypoglycemic and hypolipidemic effects in diabetic rats by mechanism(s) which appear to be similar to that of taurine, which involve insulin sensitization or an insulin-like effect. The identity and the exact mechanism(s) of action of the active component(s) of the AI-extract are not known. Ajuga iva appears to be a useful plant in the therapy of diabetes, a condition in which hyperglycemia and dyslipidemia coexist quite often.

  2. Efficacy and safety of modified Yale insulin infusion protocol in Japanese diabetic patients after open-heart surgery.

    PubMed

    Tamaki, Motoyuki; Shimizu, Tomoaki; Kanazawa, Akio; Tamura, Yoshifumi; Hanzawa, Ayame; Ebato, Chie; Itou, Chiharu; Yasunari, Eisuke; Sanke, Haruna; Abe, Hiroko; Kawai, Junko; Okayama, Kaede; Matsumoto, Kazuhisa; Komiya, Koji; Kawaguchi, Minako; Inagaki, Noriko; Watanabe, Takahiro; Kanazawa, Yoshie; Hirose, Takahisa; Kawamori, Ryuzo; Watada, Hirotaka

    2008-09-01

    To our knowledge, there is currently no insulin infusion protocol for critically ill patients especially designed for Asian diabetics although many such protocols are used in Western countries. In this study, we modified the Yale insulin infusion protocol taking into consideration the characteristics of Japanese diabetics and hospital environment. We tested the modified protocol in 40 type 2 diabetic patients after elective open-heart surgery (MY group) comparing with 35 type 2 diabetic patients under empirical blood glucose control (EC group). Analyses of 1656 blood glucose measurements during insulin infusion revealed that percentage of samples that showed achievement of target blood glucose level (80-140 mg/dl) was higher under MY (78+/-15%, n=870) than EC (57+/-23%, n=786, p<0.0001). On the other hand, the percentage of samples in which blood glucose was less than 60 mg/dl was comparable in the two groups (MY: 0.5+/-5.9 per thousand, EC: 5.1+/-18.5 per thousand). None of the patients with hypoglycemia showed significant clinical adverse effects. In conclusion, our modified Yale insulin infusion protocol is effective and safe for tight blood glucose control in Japanese diabetic patients after open-heart surgery.

  3. [Assessment of the usefulness to use a software supervising continuous infusion rates of drugs administered with pumps in ICU and estimation of the frequency of rate of administration errors].

    PubMed

    Cayot-Constantin, S; Constantin, J-M; Perez, J-P; Chevallier, P; Clapson, P; Bazin, J-E

    2010-03-01

    To assess the usefulness and the feasibility to use a software supervising continuous infusion rates of drugs administered with pumps in ICU. Follow-up of practices and inquiry in three intensive care units. Guardrails software(TM) of reassurance of the regulations of the rates of pumps (AsenaGH, Alaris). First, evaluation and quantification of the number of infusion-rates adjustments reaching the maximal superior limit (considered as infusion-rate-errors stopped by the software). Secondly, appreciate the acceptance by staffs to such a system by a blinded questionnaire and a quantification of the number of dataset pumps programs performed with the software. The number of administrations started with the pumps of the study in the three services (11 beds) during the period of study was 63,069 and 42,694 of them (67.7 %) used the software. The number of potential errors of continuous infusion rates was 11, corresponding to a rate of infusion-rate errors of 26/100,000. KCl and insulin were concerned in two and five cases, respectively. Eighty percent of the nurses estimated that infusion-rate-errors were rare or exceptional but potentially harmful. Indeed, they considered that software supervising the continuous infusion rates of pumps could improve safety. The risk of infusion-rate-errors of drugs administered continuously with pump in ICU is rare but potentially harmful. A software that controlled the continuous infusion rates could be useful. Copyright (c) 2010 Elsevier Masson SAS. All rights reserved.

  4. Feasibility, efficacy, and safety of a simple insulin infusion protocol in a large volume cardiac surgery unit in India.

    PubMed

    Bansal, Beena; Mithal, Ambrish; Carvalho, Pravin; Mehta, Yatin; Trehan, Naresh

    2015-01-01

    Inpatient hyperglycemia management is essential, but difficult to achieve especially in a large volume cardiac surgery setup, thus necessitating use of nurse-led insulin protocols. A rapid flux of nurses dealing with a huge workload has been a cause for traditionally not using nurse-led protocols in most Indian institutes. The challenges we faced were to have a simple protocol for the nurses to accept it without compromising on glycemic control. Therefore, this observational study was planned to measure the efficacy and safety of the insulin infusion protocol in cardiac surgery patients. Insulin protocol was implemented, using seven fixed columns of infusion with the nurse making decisions to initiate and titrate doses based on simple rules. Blood glucose (BG) data captured from blood gas analyzers (glucometrics) in the intervention group (i.e., after protocol implementation) were compared to control group (i.e., before the protocol implementation). The mean BG for the first 48 h was lower in the intervention group as compared to control group, without an increase in the episodes of hypoglycemia. The nurses found the protocol easy to understand, less time-consuming and there was no protocol deviation over 8 months after implementation. A small change in the process, allowing nurses to titrate insulin doses based on some rules and having seven fixed columns of insulin infusion rates, improved glycemic control and efficiency.

  5. Continuous infusion of porcine factor VIII: stability, microbiological safety and clinical experience.

    PubMed

    DiMichele, D M; Gorman, P O; Kasper, C K; Mannucci, P M; Santagostino, E; Hay, C R M

    2002-01-01

    Porcine factor VIII (pFVIII) is an effective haemostatic treatment for bleeding in selected patients with FVIII inhibitors. Its use is sometimes associated with a transient fall in platelet count and transfusion reactions, the risk of which may be related to the rate of administration. Theoretical considerations suggest that the administration of pFVIII by continuous infusion should be effective, and could have pharmacokinetic advantages that lead to an improvement in the side-effect profile. The results of a retrospective survey of continuous infusion of pFVIII with respect to clinical safety and efficacy are reported. Porcine FVIII stability and microbiological studies are included. It is concluded that pFVIII given by continuous infusion is safe and effective. The risk of transfusion reactions and fall in platelet count appears to be reduced, compared with bolus administration. Stability studies showed that pFVIII activity declined at room temperature, most rapidly in the dilute solution (5-10 U mL(-1)). More concentrated mixtures showed acceptable stability for up to 24 h using a variety of infusion devices. Various concentrations of pFVIII did not support the growth of Escherichia coli or Staphylococcus aureus. These observations suggest that the porcine factor is suitable for continuous infusion (CI).

  6. A comparison of continuous infusion of vecuronium and atracurium in midline and paramedian laparotomies.

    PubMed

    Chaudhari, L S; Shetty, A N; Buddhi, M; Krishnan, G

    1999-01-01

    This was a study to compare continuous intravenous infusion of atracurium with continuous intravenous infusion of vecuronium for intraoperative muscle relaxation in 62 ASA I / II patients. Scheduled for laparotomies and pelvic surgeries under general anaesthesia. They were randomly allocated in two groups to receive either vecuronium infusion of 50 microg/kg/hour following a bolus dose of 0.1 microg/kg, or atracurium infusion of 400 microg/kg/hour following a bolus dose of 0.5 microg/kg. The mean infusion dose of atracurium was 478 +/- 44.11 microg/kg/hour and that of vecuronium was 63.2 +/- 74 microg/kg/hour for adequate muscle relaxation. The depth of neuromuscular blockade was monitored by using peripheral nerve stimulator so that only one twitch of train of four was present, resistance to ventilation, surgical relaxation and haemodynamic changes. Vecuronium infusions produced more haemodynamic stability than atracurium infusions. Vecuronium produced lesser change in systolic blood pressure (mean change of 3. 46 +/- 3.33%) from baseline values as compared to atracurium (mean change of 5.81 +/- 3.73%) from baseline values ( p < 0.01) which was statistically significant. The difference in mean pulse rate change from baseline value in the atracurium group (4.78 +/- 2.745%) was less than that in the vecuronium group (5.99 +/- 2.67%), which was not statistically significant. Spontaneous recovery was faster with vecuronium (540.94 +/- 76.46 seconds) as compared to atracurium (596. 33 +/- 72.48 seconds). 84.4% of patients who received vecuronium fell within good to very good category of muscle relaxation as compared to 63.3% in atracurium group. There were no cost benefits when either agents were used in infusion form.

  7. Continuous s.c. infusion rather than twice-daily injections of IGF-I more effectively increases serum IGF binding protein-3 in female monkeys.

    PubMed

    Wilson, M E; Lackey, S L

    1999-09-01

    In order to better understand how the IGF-I axis is affected by exogenous IGF-I, this study compared the effects of a constant s.c. infusion of IGF-I with that of twice-daily injections of IGF-I in young adult female rhesus monkeys. Clinical studies suggest that circulating concentrations of insulin-like growth factor binding protein-3 (IGFBP-3) are decreased or unaffected by IGF-I administration, whereas acute increases in IGF-I may increase serum IGFBP-1. However, studies in monkeys indicate that acute or continuous infusion of IGF-I effectively increases serum IGFBP-3. Female monkeys were studied for 5 days with no IGF-I supplementation (baseline) and for 5 days of IGF-I treatment by either constant infusion (120 microg/kg per day s.c., n = 5) or twice-daily injections of IGF-I (60 microg/kg per injection s.c., n = 5). Serum samples were collected daily at 0800 h and at 0800, 0900, 1100, 1500, and 2000 h on days 1 and 4 for each condition. Samples were assayed for IGF-I, IGFBPs-1 and -3, insulin, and glucose. Serum IGF-I was consistently increased above baseline within 24 h of the initiation of constant infusion, but was delayed until the second day of treatment in the injection group. Serum IGFBP-3 followed the pattern of IGF-I, with concentrations increased by day 1 during constant infusion and by day 2 during intermittent injections. Although both treatments effectively increased serum IGFBP-3, the increase was greater during constant infusion (31% above baseline) compared with injection (17%). Immunoblotting revealed that the constant infusion of IGF-I resulted in quantitatively more lower-molecular-mass fragments of IGFBP-3 than were observed during baseline or intermittent injections. Size-exclusion chromatography and ultrafiltration indicated that most IGFBP-3 was found in the ternary complex, with a greater percentage found in the ternary complex during baseline (90%) than during constant infusion (86%) or intermittent injections of IGF-I (87%). In

  8. Combined Pioglitazone and Metformin Treatment Maintains the Beneficial Effect of Short-Term Insulin Infusion in Patients with Type 2 Diabetes: Results from a Pilot Study

    PubMed Central

    Musholt, Petra B.; Schöndorf, Thomas; Pfützner, Andreas; Hohberg, Cloth; Kleine, Iris; Fuchs, Winfried; Hehenwarter, Silvia; Dikta, Gerhard; Kerschgens, Benedikt; Forst, Thomas

    2009-01-01

    Background The aim of our study was to examine the efficacy of short-term intravenous insulin intervention followed by oral pioglitazone/metformin therapy to prevent patients from continuous insulin application. Methods This prospective, open-label, 4-month pilot study comprised of 14 diabetes patients (5 female, 9 male; age 60 ± 2 years; body mass index 29 ± 3.2 kg/m2; hemoglobin A1c [HbA1c] 7.6 ± 1.1%) with (1) insufficient glycemic control under a dose of metformin ≥1700 mg/day and/or metformin plus additional oral antidiabetes drugs (OADs) and (2) appropriate residual β-cell function. Initially, an inpatient 34 h continuous intravenous insulin infusion was performed, and metformin was given (2x 850 mg/day). Insulin was stopped, and pioglitazone 30 mg/day was added at the second inpatient day. Patients were followed for four months. Efficacy parameters [change of HbA1c, fasting blood glucose [FBG], intact proinsulin, adiponectin, and high-sensitivity C-reactive protein (hsCRP)] were assessed after initial normalization of blood glucose values by intravenous insulin and at the study end point. Results During the acute insulin intervention, FBG levels were stabilized in all study subjects. In the following OAD treatment period, five patients showed an improvement of HbA1c > 0.5% [35.7%; seven patients remained stable (50.0%), two patients were nonresponders (14.3%)]. Fasting glucose values dropped after insulin infusion (-17.7%; p < .001). This effect was maintained during the consecutive OAD treatment period (glucose +0.3%, not significant (NS); HbA1c -6.0%; p < .05). The initial decrease in fasting intact proinsulin levels was also maintained during the study (end value -41%, p < .05). Improvements in hsCRP values (postinsulin value, -15%, NS; end value -37%; p < .05) and adiponectin values (postinsulin value +15%, NS; end value +128%; p < .001) were demonstrated at end point only after continued glitazone intake. Conclusions Our pilot study demonstrated

  9. Analysis of 72-Hour Sterility of Common Pediatric Continuous Intravenous Infusions

    PubMed Central

    Piro, Christina C.; Davis, Jennifer; Frelix, Arlesia; Grisso, Alison G.; Sinclair-Pingel, Julie; Willingham, Harold; Wright, Lorianne; Potts, Amy L.

    2009-01-01

    OBJECTIVES Patient morbidity and mortality associated with contaminated and improperly prepared sterile products has captured national attention. In response, both the United States Pharmacopeia (USP) and Centers for Disease Control (CDC) have published recommendations in an effort to minimize the risk of infection. While the CDC recommends that administration sets are not changed more frequently than every 72 hours, the USP recommends a maximum beyond use date of 48 hours. Neither organization provides specific guidance on expiration dating once the intravenous drug is dispensed. Likewise, neither addresses the length of time that a bag containing medication for continuous infusion may hang once administration to the patient has begun. We evaluated the sterility of medications that are commonly administered by continuous infusion to pediatric patients. Because frequent manipulation of infusion and administration sets may predispose the patient to adverse events, we evaluated sterility for extended beyond use dating up to 72 hours. METHODS Thirty-five common intravenous (IV) continuous infusions using 94 standard concentrations and diluents were identified. IV solutions were mixed using sterile technique in the laminar flow hood in accordance with USP guidelines. Medications were excluded for short stability, short durations of use or high cost. A sample from each solution was tested for contamination or bacterial growth at 72 hours. Any visible discoloration suggesting physical instability was also evaluated. RESULTS None of the syringes or chambers resulted in contamination, bacterial growth or discoloration after 72 hours. CONCLUSIONS This study provides sufficient data that these compounded sterile products may be stored using a beyond use date up to 72 hours for a number of commonly used continuous IV infusions in pediatric patients. In our institution, this allows for a more convenient and consistent change of both administration sets and continuous infusions

  10. Analysis of 72-hour sterility of common pediatric continuous intravenous infusions.

    PubMed

    Piro, Christina C; Davis, Jennifer; Frelix, Arlesia; Grisso, Alison G; Sinclair-Pingel, Julie; Willingham, Harold; Wright, Lorianne; Potts, Amy L

    2009-01-01

    Patient morbidity and mortality associated with contaminated and improperly prepared sterile products has captured national attention. In response, both the United States Pharmacopeia (USP) and Centers for Disease Control (CDC) have published recommendations in an effort to minimize the risk of infection. While the CDC recommends that administration sets are not changed more frequently than every 72 hours, the USP recommends a maximum beyond use date of 48 hours. Neither organization provides specific guidance on expiration dating once the intravenous drug is dispensed. Likewise, neither addresses the length of time that a bag containing medication for continuous infusion may hang once administration to the patient has begun. We evaluated the sterility of medications that are commonly administered by continuous infusion to pediatric patients. Because frequent manipulation of infusion and administration sets may predispose the patient to adverse events, we evaluated sterility for extended beyond use dating up to 72 hours. Thirty-five common intravenous (IV) continuous infusions using 94 standard concentrations and diluents were identified. IV solutions were mixed using sterile technique in the laminar flow hood in accordance with USP guidelines. Medications were excluded for short stability, short durations of use or high cost. A sample from each solution was tested for contamination or bacterial growth at 72 hours. Any visible discoloration suggesting physical instability was also evaluated. None of the syringes or chambers resulted in contamination, bacterial growth or discoloration after 72 hours. This study provides sufficient data that these compounded sterile products may be stored using a beyond use date up to 72 hours for a number of commonly used continuous IV infusions in pediatric patients. In our institution, this allows for a more convenient and consistent change of both administration sets and continuous infusions at 72 hours to potentially minimize

  11. Performance and Acceptability of a Combined Device for Insulin Infusion and Glucose Sensing in the Home Setting

    PubMed Central

    Nørgaard, Kirsten; Shin, John; Welsh, John B.; Gjessing, Hans

    2015-01-01

    Background: The use of sensor-augmented insulin pump (SAP) therapy is increasing. Currently, glucose sensors and insulin infusion cannulas are inserted separately. A new device, MiniMed Duo, combines sensing and infusion capabilities on the same platform and is intended to simplify device insertion and site management. We evaluated the device’s performance with respect to insulin delivery and glucose sensing, and its acceptability with patients. Methods: Forty-five patients (mean ± SD age, 45.5 ± 10.9 years, 48% female) with type 1 diabetes and previous use of SAP participated. Each subject was to wear 5 devices connected to insulin pumps over 15 days (3 days/device) and test capillary blood glucose (SMBG) 7 times/day. The primary endpoint was the percentage of sensor-SMBG paired values within 20% of one another. Subject experiences were assessed via questionnaires. Results: Overall, 74.8% of sensor-SMBG paired values were within 20%, meeting the primary accuracy endpoint, and the mean absolute relative difference was 15.5 ± 17.1%. Consensus error grid analysis showed that >95% of points were within the A+B zones, exceeding the threshold for adequate clinical accuracy. Insulin dosage and SMBG values did not change significantly compared to prestudy values. The functional survival of the device entering day 3 was 90.5%. There were no serious adverse events. Mean questionnaire results indicated overall satisfaction with the device. Conclusion: Duo provided insulin infusion and glucose sensing capabilities in a single device, which provided accurate glucose readings during routine use, was safe to wear, and was acceptable to most patients. It may improve satisfaction and convenience for patients using sensor-augmented insulin pumps. PMID:25591857

  12. Performance and acceptability of a combined device for insulin infusion and glucose sensing in the home setting.

    PubMed

    Nørgaard, Kirsten; Shin, John; Welsh, John B; Gjessing, Hans

    2015-03-01

    The use of sensor-augmented insulin pump (SAP) therapy is increasing. Currently, glucose sensors and insulin infusion cannulas are inserted separately. A new device, MiniMed Duo, combines sensing and infusion capabilities on the same platform and is intended to simplify device insertion and site management. We evaluated the device's performance with respect to insulin delivery and glucose sensing, and its acceptability with patients. Forty-five patients (mean ± SD age, 45.5 ± 10.9 years, 48% female) with type 1 diabetes and previous use of SAP participated. Each subject was to wear 5 devices connected to insulin pumps over 15 days (3 days/device) and test capillary blood glucose (SMBG) 7 times/day. The primary endpoint was the percentage of sensor-SMBG paired values within 20% of one another. Subject experiences were assessed via questionnaires. Overall, 74.8% of sensor-SMBG paired values were within 20%, meeting the primary accuracy endpoint, and the mean absolute relative difference was 15.5 ± 17.1%. Consensus error grid analysis showed that >95% of points were within the A+B zones, exceeding the threshold for adequate clinical accuracy. Insulin dosage and SMBG values did not change significantly compared to prestudy values. The functional survival of the device entering day 3 was 90.5%. There were no serious adverse events. Mean questionnaire results indicated overall satisfaction with the device. Duo provided insulin infusion and glucose sensing capabilities in a single device, which provided accurate glucose readings during routine use, was safe to wear, and was acceptable to most patients. It may improve satisfaction and convenience for patients using sensor-augmented insulin pumps.

  13. Dialysis Access Graft Thrombolysis: Randomized Study of Pulse-Spray Versus Continuous Urokinase Infusion

    SciTech Connect

    Goodwin, Scott C.; Arora, Lokesh C.; Razavi, Mahmood K.; Sayre, James; McNamara, Thomas O.; Yoon, Chun

    1998-03-15

    Purpose: To compare pulse-spray to continuous-infusion thrombolysis with high-dose urokinase in thrombosed dialysis access grafts. Methods: A prospective randomized controlled trial was performed. From August 1992 to September 1993, 30 thrombosed polytetrafluoroethylene (PTFE) grafts in 24 patients were included, 15 grafts in each group. The success of thrombolysis, mean time to thrombolysis, mean urokinase dose, and 60-day patency rate were evaluated. Results: In the pulse-spray group, the mean time to thrombolysis was 72 min with a mean urokinase dose of 560,000 U. The 60-day patency rate was 71%. In the continuous-infusion group, the mean infusion time to thrombolysis was 55 min with a mean dose of 479,000 U. The 60-day patency rate was 73%. Conclusion: No statistically significant difference was found between the two techniques in the mean time to thrombolysis, the mean urokinase dose used, or the 60-day patency rate.

  14. Vancomycin-associated nephrotoxicity: A meta-analysis of administration by continuous versus intermittent infusion.

    PubMed

    Hanrahan, Timothy; Whitehouse, Tony; Lipman, Jeffrey; Roberts, Jason A

    2015-09-01

    Vancomycin is a glycopeptide antibiotic widely used in the management of meticillin-resistant Staphylococcus aureus (MRSA). Guidelines currently recommend vancomycin be administered by intermittent infusion, despite recent research suggesting that continuous infusion (CI) may be associated with lower rates of vancomycin-associated nephrotoxicity. In 2012, Cataldo et al. presented a meta-analysis supporting the use of CI. Here we present an updated meta-analysis, inclusive of a recently published large-scale retrospective study. PubMed, EMBASE and Cochrane Reviews databases were searched using the keywords 'vancomycin' and 'continuous' or 'intermittent' or 'infusion' or 'discontinuous' or 'administration'. Seven studies were included in the final analysis. Using a random-effects model, a non-significant trend of reduced nephrotoxicity in those who received vancomycin by CI (risk ratio=0.799, 95% confidence interval 0.523-1.220; P=0.299) was identified. A large, randomised controlled trial is necessary to confirm these results.

  15. Deregulation of Hepatic Insulin Sensitivity Induced by Central Lipid Infusion in Rats Is Mediated by Nitric Oxide

    PubMed Central

    Marsollier, Nicolas; Kassis, Nadim; Mezghenna, Karima; Soty, Maud; Fioramonti, Xavier; Lacombe, Amélie; Joly, Aurélie; Pillot, Bruno; Zitoun, Carine; Vilar, José; Mithieux, Gilles; Gross, René; Lajoix, Anne-Dominique; Routh, Vanessa; Magnan, Christophe; Cruciani-Guglielmacci, Céline

    2009-01-01

    Background Deregulation of hypothalamic fatty acid sensing lead to hepatic insulin-resistance which may partly contribute to further impairment of glucose homeostasis. Methodology We investigated here whether hypothalamic nitric oxide (NO) could mediate deleterious peripheral effect of central lipid overload. Thus we infused rats for 24 hours into carotid artery towards brain, either with heparinized triglyceride emulsion (Intralipid, IL) or heparinized saline (control rats). Principal Findings Lipids infusion led to hepatic insulin-resistance partly related to a decreased parasympathetic activity in the liver assessed by an increased acetylcholinesterase activity. Hypothalamic nitric oxide synthases (NOS) activities were significantly increased in IL rats, as the catalytically active neuronal NOS (nNOS) dimers compared to controls. This was related to a decrease in expression of protein inhibitor of nNOS (PIN). Effect of IL infusion on deregulated hepatic insulin-sensitivity was reversed by carotid injection of non selective NOS inhibitor NG-monomethyl-L-arginine (L-NMMA) and also by a selective inhibitor of the nNOS isoform, 7-Nitro-Indazole (7-Ni). In addition, NO donor injection (L-arginine and SNP) within carotid in control rats mimicked lipid effects onto impaired hepatic insulin sensitivity. In parallel we showed that cultured VMH neurons produce NO in response to fatty acid (oleic acid). Conclusions/Significance We conclude that cerebral fatty acid overload induces an enhancement of nNOS activity within hypothalamus which is, at least in part, responsible fatty acid increased hepatic glucose production. PMID:19680547

  16. Changes of glucose, insulin and glucagon associated with propionate infusion and vitamin B-12 status in sheep.

    PubMed

    Peters, J P; Bergman, E N; Elliot, J M

    1983-06-01

    The effect of propionate on hormonal and metabolic events was studied in ewes that were vitamin B-12 depleted (de-B12) and repleted (re-B12). Experiments were conducted before and after hydroxocobalamin resupplementation. De-B12 sheep had greater blood concentrations and total hepatic influx and efflux of glucose. However, rates of net hepatic release of glucose were similar. Comparable glucagon concentrations and fluxes were reduced in de-B12, but insulin values were unaffected by vitamin B-12 status. Intramesenteric infusion of propionate elevated concentrations of glucose, insulin and glucagon at nearly all samplings. Secretion of insulin was elevated at the first sampling only (15 minutes), while glucagon appeared elevated until 30 minutes. Rates of hepatic removal of hormones were not altered during infusion. Net hepatic release of glucose was increased at nearly all samplings, but de-B12 ewes had a greater increment of total hepatic influx and efflux. De-B12 ewes exhibited a diminished glucagon response to propionate infusion, whereas insulin concentrations and hepatic uptakes tended to be greater. Vitamin B-12 status, within the range usually considered normal, thus influences metabolic and hormonal responses to increased rates of propionate entry in the sheep, independent of feed intake.

  17. CREATING AND AUDITING A NEW ELECTRONIC CONTINUOUS INFUSION PRESCRIPTION CHART FOR A PAEDIATRIC CRITICAL CARE UNIT.

    PubMed

    Siu, Emily; Sadasivam, Kalaimaran; Christiansen, Nanna

    2016-09-01

    Prescription errors, including continuous infusion prescriptions are one major source of concern in the paediatric population. Evidence suggests that use of an electronic or web-based calculator could minimise these errors. In our paediatric critical care unit (PCCU) we have created an electronic continuous infusion prescription chart to target errors in this area and conducted an audit to assess its effect on error reduction. To create an electronic continuous infusion prescription chart and audit its effect on prescription errors. Similar electronic continuous infusion prescription charts were evaluated. A Choice of electronic formats were considered and excel was chosen for its simplicity and flexibility. The choice of medications to be included, dilution method, and dosage range was agreed between PCCU consultant, pharmacy and nursing staff. Formulas for calculating each medication infusion was created and validated for different age and weight ranges by at least 2 PCCU trained pharmacists, accounting for capping at certain age and weight bands as appropriate for the medication. These were programmed into the spreadsheet for automatic calculation using inputted age and weight for the selected medications. Continuous infusion prescriptions were audited 6 months before and after implementation in April 2015 of this electronic chart. Parameters audited include medication dose, infusion rate, concentration, route, legibility, and missing or incorrect patient details. A trial period of 4 weeks preceded implementation. The electronic continuous infusion prescription form was created and used on PCCU. Hand written prescriptions had higher error rate (30.7%) as compared to electronic charts (0.7%) with a p-value <0.002. No errors were found in electronic prescriptions in regards to dose, volume and rate calculation. The use of an electronic continuous infusion prescription chart has been successfully set up and used on PCCU. Its use has significantly reduced continuous

  18. Vascular Access System for Continuous Arterial Infusion of a Protease Inhibitor in Acute Necrotizing Pancreatitis

    SciTech Connect

    Ganaha, Fumikiyo; Yamada, Tetsuhisa; Yorozu, Naoya; Ujita, Masuo; Irie, Takeo; Fukuda, Yasushi; Fukuda, Kunihiko; Tada, Shimpei

    1999-09-15

    We used a vascular access system (VAS) for continuous arterial infusion (CAI) of a protease inhibitor in two patients with acute necrotizing pancreatitis. The infusion catheter was placed into the dorsal pancreatic artery in the first patient and into the gastroduodenal artery in the second, via a femoral artery approach. An implantable port was then connected to the catheter and was secured in a subcutaneous pocket prepared in the right lower abdomen. No complications related to the VAS were encountered. This system provided safe and uncontaminated vascular access for successful CAI for acute pancreatitis.

  19. Phase I trial of 96-hour continuous infusion of dexrazoxane in patients with advanced malignancies.

    PubMed

    Tetef, M L; Synold, T W; Chow, W; Leong, L; Margolin, K; Morgan, R; Raschko, J; Shibata, S; Somlo, G; Yen, Y; Groshen, S; Johnson, K; Lenz, H J; Gandara, D; Doroshow, J H

    2001-06-01

    Dexrazoxane is a bidentate chelator of divalent cations. Pretreatment with short infusions of dexrazoxane prior to bolus doxorubicin has been shown to lessen the incidence and severity of anthracycline-associated cardiac toxicity. However, because of rapid, diffusion-mediated cellular uptake and the short plasma half-life of dexrazoxane, combined with prolonged cellular retention of doxorubicin, dexrazoxane may be more effective when administered as a continuous infusion. Thus, a Phase I pharmacokinetic trial of a 96-h infusion of dexrazoxane was performed. Dexrazoxane doses were escalated in cohorts of 3 to 6 patients per dose level. All patients received granulocyte-colony stimulating factor at a dose of 5 microg/kg/day starting 24 h after completion of the dexrazoxane infusion. Plasma samples were collected and analyzed for dexrazoxane by high-performance liquid chromatography. Urine collections were performed at baseline and during the infusion to determine the renal clearance of dexrazoxane and the excretion rate of divalent cations. Twenty-two patients were enrolled at doses ranging from 125 to 250 mg/m(2)/day. Grade 3 and 4 toxicities included grade 4 thrombocytopenia in 2 patients treated at 250 mg/m(2)/day, grade 3 thrombocytopenia and grade 4 nausea and vomiting in 1 patient treated at 221 mg/m(2)/day, grade 4 diarrhea and grade 3 nausea and vomiting in 1 patient treated at 221 mg/m(2)/day, and grade 3 hypertension in 1 patient treated at 166.25 mg/m(2)/day. Steady-state dexrazoxane levels ranged from 496 microg/l (2.2 microM) to 1639 microg/l (7.4 microM). Dexrazoxane plasma CL(ss) and elimination t(1/2) were 7.2 +/- 1.6 l/h/m(2) and 2.0 +/- 0.8 h, respectively. The mean percentage of administered dexrazoxane recovered in the urine at steady state was 30% (range, 10-66%). Urinary iron and zinc excretion during the dexrazoxane infusion increased in 12 of 18 and 19 of 19 patients by a median of 3.7- and 2.4-fold, respectively. These results suggest that

  20. Continuous infusion of levodopa-carbidopa intestinal gel in Parkinson's disease.

    PubMed

    Guthikonda, Lalitha N; Lyons, Kelly E; Pahwa, Rajesh

    2014-07-01

    Evaluation of: Olanow CW, Kieburtz K, Odin P et al. Continuous intrajejunal infusion of levodopa-carbidopa intestinal gel for patients with advanced Parkinson's disease: a randomised, controlled, double-blind, double-dummy study. Lancet Neurol. 13(2), 141-149 (2014). Levodopa-induced motor complications, including motor fluctuations and dyskinesia, can be a major source of disability for Parkinson's disease patients. The development of levodopa-induced motor complications has been attributed to the pulsatile dopaminergic stimulation characteristic of conventional oral levodopa regimens. This is a review of a 12-week, randomized, controlled, double-blind, double-dummy study of continuous jejunal infusion of levodopa-carbidopa intestinal gel to determine if the continuous infusion of levodopa reduces motor complications in Parkinson's disease. Results demonstrated that levodopa-carbidopa intestinal gel significantly reduced off-time without increasing troublesome dyskinesia compared with standard oral levodopa therapy. Adverse effects were common in both the levodopa-carbidopa intestinal gel and placebo groups and were related primarily to the infusion hardware.

  1. Pros and cons of apomorphine and L-dopa continuous infusion in advanced Parkinson's disease.

    PubMed

    Antonini, Angelo; Odin, Per

    2009-12-01

    Motor fluctuations and dyskinesia are common in advanced Parkinson's disease and can be poorly managed by current oral medications. Risk factors include the amount of L-dopa administered, gender and patient age. Continuous duodenal L-dopa or subcutaneous apomorphine infusions are helpful strategies because they can control motor complications by providing continuous dopaminergic drug delivery. Apomorphine subcutaneous infusion provides a motor benefit similar to that of dopamine and is relatively easy to use in advanced PD. However, it commonly requires concomitant administration of oral L-dopa and its long-term use is limited by compliance. Continuous administration of L-dopa/carbidopa by infusion in the duodenum/jejunum is a more complex procedure requiring a gastrostomy for the placement of the infusion tube, but it allows replacement of all oral medications and the achievement of a satisfactory therapeutic response paralleled by a reduction of motor complication severity. It should be noted that although these procedures are effective, most evidence relates to small case series and, particularly in the case of apomorphine, despite its long-term availability, there is a complete lack of randomized blinded studies. In addition, unlike deep brain stimulation, it is unclear which patients are the best candidates for these procedures, making any indirect comparison very complex, given the clinical heterogeneity of reported patients. This has consequences in resource allocation and in estimating cost-benefit ratios for these complex therapies in advanced PD. Copyright 2009 Elsevier Ltd. All rights reserved.

  2. Continuous-Infusion Etomidate in a Patient Receiving Extracorporeal Membrane Oxygenation

    PubMed Central

    Desselle, Bonnie; Rossi, Janet L.

    2017-01-01

    We describe a 16-year-old, 65-kg male deployed on extracorporeal membrane oxygenation (ECMO) for refractory respiratory failure secondary to ingestion of multiple substances. During his ECMO course, standard sedative and analgesic strategies failed and alternative medications were used. The patient received various dosages of fentanyl, morphine, hydromorphone, clonidine patches, dexmedetomidine, lorazepam, methadone, pentobarbital, olanzapine, and propofol. Despite administration of multiple agents, on day 29 of ECMO the patient experienced elevated blood pressures due to agitation, and continuous infusion etomidate was started. At the time of etomidate initiation, the osmolar gap was 8 mOsm/kg. During etomidate therapy, the blood pressure remained normal, sedative agents were slowly weaned, and the patient required few PRN medications. On day 6 of etomidate, the osmolar gap increased to 127 mOsm/kg and etomidate was discontinued. Continuous-infusion ketamine was started, but the blood pressure was not controlled. Metabolic acidosis is a known side effect of etomidate due to inclusion of propylene glycol as a pharmaceutical solvent in the formulation. Despite high-dose etomidate (20 mcg/kg/min) for approximately 6 days, our patient did not experience metabolic acidosis. Absence of this adverse effect caused us to question the role of the ECMO circuit. To our knowledge, this is the first report of the use of continuous-infusion etomidate during ECMO. Etomidate infusion could be considered in difficult-to-manage patients after other alternatives have failed. PMID:28337083

  3. Continuous-Infusion Etomidate in a Patient Receiving Extracorporeal Membrane Oxygenation.

    PubMed

    LaRochelle, Joseph M; Desselle, Bonnie; Rossi, Janet L

    2017-01-01

    We describe a 16-year-old, 65-kg male deployed on extracorporeal membrane oxygenation (ECMO) for refractory respiratory failure secondary to ingestion of multiple substances. During his ECMO course, standard sedative and analgesic strategies failed and alternative medications were used. The patient received various dosages of fentanyl, morphine, hydromorphone, clonidine patches, dexmedetomidine, lorazepam, methadone, pentobarbital, olanzapine, and propofol. Despite administration of multiple agents, on day 29 of ECMO the patient experienced elevated blood pressures due to agitation, and continuous infusion etomidate was started. At the time of etomidate initiation, the osmolar gap was 8 mOsm/kg. During etomidate therapy, the blood pressure remained normal, sedative agents were slowly weaned, and the patient required few PRN medications. On day 6 of etomidate, the osmolar gap increased to 127 mOsm/kg and etomidate was discontinued. Continuous-infusion ketamine was started, but the blood pressure was not controlled. Metabolic acidosis is a known side effect of etomidate due to inclusion of propylene glycol as a pharmaceutical solvent in the formulation. Despite high-dose etomidate (20 mcg/kg/min) for approximately 6 days, our patient did not experience metabolic acidosis. Absence of this adverse effect caused us to question the role of the ECMO circuit. To our knowledge, this is the first report of the use of continuous-infusion etomidate during ECMO. Etomidate infusion could be considered in difficult-to-manage patients after other alternatives have failed.

  4. [Prevention of psychedelic side effects associated with low dose continuous intravenous ketamine infusion].

    PubMed

    Remerand, Francis; Couvret, Claude; Pourrat, Xavier; Le Tendre, Charlotte; Baud, Annick; Fusciardi, Jacques

    2007-01-01

    Continuous low dose infusion of intravenous ketamine for postoperative analgesia was often associated with frightening acute psychodysleptic experiences in our patients. We hypothesized they were due to boluses of ketamine accumulated in the infusion line. We evaluated on two successive groups the impact of perfusion line modifications on psychodysleptic side effects occurrence. We compared a reference historic group (in which ketamine line was connected to perfusion line) to a second prospective group (in which ketamine line was connected to the venous catheter via an unidirectional valve). Psychodysleptic experiences occurrence decreased from 4 patients of 26 (15%) to 2 of 116 (2%, p = 0.01). Moreover, these experiences were no longer associated with severe anxious symptoms like near death experiences. An unidirectional valve must be considered to limit the occurrence of low dose intravenous ketamine infusion associated psychedelic side effects, during postoperative analgesia.

  5. Continuous subcutaneous infusion of lidocaine for persistent hiccup in advanced cancer.

    PubMed

    Kaneishi, Keisuke; Kawabata, Masahiro

    2013-03-01

    Persistent hiccup can cause anorexia, weight loss, disabling sleep deprivation, anxiety, and depression. Therefore, relief of persistent hiccup is important for advanced cancer patients and their family. Most reports on this condition are case series reports advocating the use of baclofen, haloperidol, gabapentin, and midazolam. However, these medications are occasionally ineffective or accompanied by intolerable side effects. The sodium channel blocker lidocaine has been shown to be effective in treating a variety of disorders thought to involve neuropathic mechanisms. Intravenous administration of lidocaine is common but efficacy has also been reported for subcutaneous infusion. In advanced cancer patients, subcutaneous infusion is easy, advantageous, and accompanied by less discomfort. We report a case of severe and sustained hiccup caused by gastric cancer that was successfully treated with a continuous subcutaneous infusion of lidocaine (480 mg (24 ml)/day) without severe side effects.

  6. Modification of the effects of continuous low dose rate irradiation by concurrent chemotherapy infusion

    SciTech Connect

    Fu, K.K.; Rayner, P.A.; Lam, K.N.

    1984-08-01

    The combined effects of continuous low dose rate irradiation (CLDRI) and concurrent infusion of bleomycin, cyclophosphamide, cis-platinum, 5-fluorouracil, actinomycin D, and mitomycin C were studied in the SCC VII/SF tumor, a squamous cell carcinoma and the jejunal crypt cells in the mouse. For the SCC VII/SF tumor, enhanced cell killing was seen with each of the six drugs when infused concurrently with CLDRI; the greatest enhancement was seen with mitomycin C and cis-platinum. For the jejunal crypt cells, enhanced cell killing was seen primarily with bleomycin. The authors results suggest a therapeutic gain with concurrent CLDRI and chemotherapy infusion for five of the six chemotherapeutic drugs studied with the exception of bleomycin.

  7. A mathematical model describing the glycemic response of diabetic patients to meal and i.v. infusion of insulin.

    PubMed

    Fabietti, P G; Calabrese, G; Iorio, M; Bistoni, S; Brunetti, P; Sarti, E; Benedetti, M M

    2001-10-01

    Nine type 1 diabetic patients were studied for 24 hours. During this period they were given three calibrated meals. The glycemia was feedback-controlled by means of an artificial pancreas. The blood concentration of glucose and the infusion speed of the insulin were measured every minute. The experimental data referring to each of the three meals were used to estimate the parameters of a mathematical model suitable for describing the glycemic response of diabetic patients at meals and at the i.v. infusion of exogenous insulin. From the estimate a marked dispersion of the parameters was found, both interindividual and intraindividual. Nevertheless the models thus obtained seem to be usable for the synthesis of a feedback controller, especially in view of creating a portable artificial pancreas that now seems possible owing to the realization (so far experimental) of sufficiently reliable glucose concentration sensors.

  8. Continuous wound infusion of local anesthetic for the control of pain after elective abdominal colorectal surgery.

    PubMed

    Polglase, Adrian L; McMurrick, Paul J; Simpson, Paul J B; Wale, Roger J; Carne, Peter W G; Johnson, William; Chee, Justin; Ooi, Corrine W; Chong, Jennifer W D; Kingsland, Sally R; Buchbinder, Rachelle

    2007-12-01

    Local anesthetic wound infusion has been investigated in recent years as a potential alternative to standard analgesic regimens after major surgery. This study investigates the efficacy of a continuous wound infusion of ropivacaine in conjunction with best practice postoperative analgesia after midline laparotomy for abdominal colorectal surgery. We performed a randomized, participant and outcome assessor-blinded, placebo-controlled trial on patients presenting for major abdominal colorectal surgery at our institution between December 2003 and February 2006. Patients were allocated to receive ropivacaine 0.54 percent or normal saline via a dual catheter Painbuster Soaker (I-Flow Corporation, OH, USA) continuous infusion device into their midline laparotomy wound for 72 hours postoperatively. A total of 310 patients were included in this study. The continuous wound infusion of ropivacaine after abdominal colorectal surgery conveys minimal benefit compared with saline wound infusion. No statistically significant difference could be shown for: pain at rest, morphine usage, length of stay, mobility, nausea, or return of bowel function. There was a small, statistically significant difference in mean pain on movement on Day 1 for the ropivacaine group (adjusted mean difference -0.6 (range, -1.08 to -0.13)). Although this trend continued on Days 2 and 3, the differences between groups were no longer statistically significant. Management of pain after major abdominal colorectal surgery is best achieved through adopting a multimodal approach to analgesia. Delivery of ropivacaine to midline laparotomy wounds via a Painbuster Soaker device is safe, but we have not demonstrated any significant clinical advantage over current best practice.

  9. Continuous compared with intermittent epidural infusion on progress of labor and patient satisfaction.

    PubMed

    Salim, Raed; Nachum, Zohar; Moscovici, Roland; Lavee, Michal; Shalev, Eliezer

    2005-08-01

    To compare continuous with intermittent epidural infusion on the duration of labor and patients' satisfaction in nulliparous women. Nulliparous women who requested epidural analgesia during labor were randomly allocated to receive either a continuous infusion of 0.125% bupivacaine with 2 microg/mL fentanyl at a rate of 8 mL/h (group A) or intermittent bolus of 10 mL of 0.25% bupivacaine on demand (group B). Controls were nulliparous women who did not receive epidural analgesia (group C). Included were singleton term pregnancies with cervical dilatation between 2 cm and 5 cm. A comparison was made between the groups regarding the duration of the active phase and the second stage of labor and patients' satisfaction. Secondary outcomes investigated were the mode of delivery, analgesia-related complications, and intrapartum and postpartum complications. Cord pH and Apgar score measured neonatal outcome. Sixty-three parturients were randomly assigned to receive continuous infusion, and 64 received intermittent bolus infusion. Sixty-three patients served as controls. Mean duration of the active phase and the second stage of labor were not statistically different between groups A and B. Each technique produced comparable analgesia, achieving equivalent maternal satisfaction, with no apparent complications. The active phase of labor was prolonged by an average of 60 minutes and the 2nd stage by an average of 36 minutes regardless of the type of epidural compared with controls. The mode of delivery and maternal and neonatal outcome were not significantly different among the 3 groups. This study provides evidence that both continuous and intermittent epidural infusion produce comparable analgesia achieving equivalent maternal satisfaction with no difference regarding the duration of labor between them. Although patients receiving epidural analgesia experienced longer labors compared with controls, both mothers and neonates were unharmed.

  10. Circulating leptin response to feeding and exogenous infusion of insulin in sheep exposed to thermoneutral and cold environments.

    PubMed

    Asakuma, S; Morishita, H; Sugino, T; Kurose, Y; Kobayashi, S; Terashima, Y

    2003-02-01

    Leptin has been shown to regulate feed intake and energy expenditure. Insulin stimulates leptin secretion in rodents, but its action on leptin secretion is still obscure in ruminants. If insulin stimulates leptin secretion in ruminants, circulating leptin concentrations may change during exposure to cold, because of fluctuating insulin secretion and action in the cold environment. The present experiment was designed to determine whether feeding or exogenous administration of insulin affects circulating leptin levels in sheep exposed to thermoneutral and cold environments. Suffolk rams that were shorn and fed a diet once daily were subjected to a thermoneutral (20 degrees C) or cold (0 degrees C) environment for at least 1 week. Overall mean concentrations of plasma leptin in the feeding experiment were lower (P<0.05) in the cold environment than in the thermoneutral environment. Plasma leptin levels remained relatively unchanged after feeding in both environments, though plasma insulin response to feeding in both environments increased (P<0.01). The euglycemic clamps (insulin infusion rate: 4 mUkgBW(-1)min(-1) for 2 h) increased (P<0.01) circulating leptin concentrations in the thermoneutral, but not in the cold environment. These results suggest that lower circulating leptin levels in ruminants exposed to the cold environment could be partly due to the depressed insulin action on leptin secretion.

  11. Effects of insulin infusion on glucose homeostasis and glucose metabolism in rainbow trout fed a high-carbohydrate diet.

    PubMed

    Polakof, S; Moon, T W; Aguirre, P; Skiba-Cassy, S; Panserat, S

    2010-12-15

    The origin for the poor glucose utilization in carnivorous fish species fed high carbohydrate diets remains under debate. In the present study, we have fed rainbow trout a diet containing 30% carbohydrate for 1 or 5 days. In both cases, fish were implanted with mini-osmotic pumps releasing 0.7 i.u. kg(-1) day(-1) bovine insulin, and mRNA transcripts and the protein phosphorylation status of proteins controlling glycemia and glucose-related metabolism were studied in fish killed 6 h after the last meal. We demonstrate that when the exposure occurs over a short term (30 h), insulin exerts beneficial actions on trout glucose homeostasis, including a lowered glycemia and increased hepatic lipogenic and glycogenic potentials. However, when trout were fed for 5 days, these beneficial actions of insulin infusion were no longer observed. Thus, the increased lipogenic potential observed after one single meal was not present, and this together with the increased glycogenesis and the decreased glucose exported to the blood from the liver explains the lack of hypoglycemic action of insulin. The fact that insulin improved glucose homeostasis when administrated over a short time period implies that endogenous insulin secretion is inadequate in trout to deal with this amount of dietary carbohydrates. Moreover, the fact that a longer exposure to insulin resulted in a reduced response indicates that the rainbow trout is sensitive to insulin, re-enforcing the hypothesis that the hyperglycemia observed following a high carbohydrate meal is an insulin secretion issue rather an insulin action issue.

  12. In Vivo Murine Model of Continuous Intramedullary Infusion of Particles – A Preliminary Study

    PubMed Central

    Ma, Ting; Ortiz, Steven G.; Huang, Zhinong; Ren, Peigen; Smith, R. Lane; Goodman, Stuart B.

    2008-01-01

    Continued production of wear debris affects both initial osseointegration and subsequent bone remodeling of total joint replacements (TJRs). However, continuous delivery of clinically relevant particles using a viable, cost effective, quantitative animal model to simulate the scenario in humans has been a challenge for orthopaedic researchers. In this study, we successfully infused blue-dyed polystyrene particles, similar in size to wear debris in humans, to the intramedullary space of the mouse femur for four weeks using an osmotic pump. Approximately 40% of the original particle load (85 ul) was delivered into the intramedullary space, an estimate of 3 × 10 9 particles. The visible blue dye carried by the particles confirmed the delivery. This model demonstrated that continuous infusion of particles to the murine bone-implant interface is possible. In vivo biological processes associated using wear debris particles can be studied using this new animal model. PMID:18777575

  13. Continuous infusion vs. bolus dosing: implications for beta-lactam antibiotics.

    PubMed

    Mohd Hafiz, Abdul-Aziz; Staatz, C E; Kirkpatrick, C M J; Lipman, J; Roberts, J A

    2012-01-01

    Beta-lactam antibiotics display time-dependant pharmacodynamics whereby constant antibiotic concentrations rather than high peak concentrations are most likely to result in effective treatment of infections caused by susceptible bacteria. Continuous administration has been suggested as an alternative strategy, to conventional intermittent dosing, to optimise beta-lactam pharmacokinetic/pharmacodynamic (PK/PD) properties. With the availability of emerging data, we elected to systematically investigate the published literature describing the comparative PK/PD and clinical outcomes of beta-lactam antibiotics administered by continuous or intermittent infusion. We found that the studies have been performed in various patient populations including critically ill, cancer and cystic fibrosis patients. Available in vitro PK/PD data conclusively support the administration of beta-lactams via continuous infusion for maximizing bacterial killing from consistent attainment of pharmacodynamic end-points. In addition, clinical outcome data supports equivalence, even with the use of a lower dose by continuous infusion. However, the present clinical data is limited with small sample sizes common with insufficient power to detect advantages in favour of either dosing strategy. With abundant positive pre-clinical data as well as document in vivo PK/PD advantages, large multi-centre trials are needed to describe whether continuous administration of beta-lactams is truly more effective than intermittent dosing.

  14. Continuous intrathecal fluid infusions elevate nerve growth factor levels and prevent functional deficits after spinal cord ischemia.

    PubMed

    Bowes, M; Tuszynski, M H; Conner, J; Zivin, J A

    2000-11-17

    Continuous intracerebroventricular or intrathecal infusions of neurotrophic factors have been reported to prevent neuronal degeneration, stimulate axonal sprouting and ameliorate behavioral deficits in various models of CNS injury and aging. In the present study, the ability of intrathecal infusions of recombinant human nerve growth factor (NGF) to reduce functional deficits following spinal cord ischemia was investigated. Adult rabbits underwent intrathecal cannulation and continuous infusions of either 300 microg/ml recombinant human NGF or artificial CSF (vehicle) at a rate of 143 microl/day for 7 days prior to induction of spinal cord ischemia. Continuous infusions were maintained after induction of ischemia. Four days later, both NGF-treated and vehicle-infused subjects showed a significant amelioration of functional motor deficits compared to lesioned, non-infused subjects (P<0.05). The average duration of tolerated ischemia increased from 23.4+/-1.8 min in lesioned, non-infused subjects to 35.5+/-3.1 min in lesioned, artificial CSF-infused subjects and 35.6+/-4.7 min in NGF-infused subjects (mean+/-S.E.M.). Significantly elevated NGF protein levels were attained within the spinal cords of both NGF-treated subjects and artificial CSF-infused subjects, although levels were substantially higher in NGF-treated subjects (9.8+/-3.8 ng/g in NGF-infused vs. 2.0+/-0.4 ng/g in vehicle-infused and only 0.4+/-0.2 ng/g in lesioned, non-infused animals). These findings indicate that the process of intrathecal cannulation and fluid infusion elicits alterations in the spinal cord environment that are neuroprotective, including spontaneous elevations in NGF levels.

  15. The Effect of Insulin Infusion on the Metabolites in Cerebral Tissues Assessed With Proton Magnetic Resonance Spectroscopy in Young Healthy Subjects With High and Low Insulin Sensitivity

    PubMed Central

    Karczewska-Kupczewska, Monika; Tarasów, Eugeniusz; Nikołajuk, Agnieszka; Stefanowicz, Magdalena; Matulewicz, Natalia; Otziomek, Elżbieta; Górska, Maria; Strączkowski, Marek; Kowalska, Irina

    2013-01-01

    OBJECTIVE Insulin may play important roles in brain metabolism. Proton magnetic resonance spectroscopy (1H-MRS) of the central nervous system gives information on neuronal viability, cellular energy, and membrane status. To elucidate the specific role of insulin action in the brain, we estimated neurometabolites with 1H-MRS and assessed their regulation by insulin infusion and their relationship with insulin sensitivity. RESEARCH DESIGN AND METHODS We studied 16 healthy young men. 1H-MRS was performed at baseline and after 240 min of euglycemic-hyperinsulinemic clamp. Voxels were positioned in the left frontal lobe, left temporal lobe, and left thalamus. The ratios of N-acetylaspartate (NAA), choline-containing compounds (Cho), myo-inositol, and glutamate/glutamine/γ-aminobutyric acid complex (Glx) to creatine (Cr) and nonsuppressed water signal were determined. The participants were divided into subgroups of high (high IS) and low (low IS) insulin sensitivity. RESULTS Baseline neurometabolic substrates were not different between the groups. Insulin infusion resulted in an increase in frontal NAA/Cr and NAA/H2O and frontal and temporal Glx/Cr and Glx/H2O and a decrease in frontal Cho/Cr and temporal Cho/H2O and myo-inositol/H2O (all P < 0.05, except temporal Glx/H2O, P = 0.054, NS) in the high-IS, but not in the low-IS, group. Insulin sensitivity correlated positively with frontal NAA/Cr and NAA/H2O and temporal Glx/H2O and negatively with temporal myo-inositol/Cr and myo-inositol/H2O assessed during the second 1H-MRS (all P < 0.05). CONCLUSIONS Insulin might influence cerebral metabolites, and this action is impaired in subjects with low whole-body insulin sensitivity. Thus, our results provide a potential link between insulin resistance and altered metabolism of the central nervous system. PMID:23596182

  16. A Multicenter Randomized Trial of Continuous versus Intermittent β-Lactam Infusion in Severe Sepsis.

    PubMed

    Dulhunty, Joel M; Roberts, Jason A; Davis, Joshua S; Webb, Steven A R; Bellomo, Rinaldo; Gomersall, Charles; Shirwadkar, Charudatt; Eastwood, Glenn M; Myburgh, John; Paterson, David L; Starr, Therese; Paul, Sanjoy K; Lipman, Jeffrey

    2015-12-01

    Continuous infusion of β-lactam antibiotics may improve outcomes because of time-dependent antibacterial activity compared with intermittent dosing. To evaluate the efficacy of continuous versus intermittent infusion in patients with severe sepsis. We conducted a randomized controlled trial in 25 intensive care units (ICUs). Participants commenced on piperacillin-tazobactam, ticarcillin-clavulanate, or meropenem were randomized to receive the prescribed antibiotic via continuous or 30-minute intermittent infusion for the remainder of the treatment course or until ICU discharge. The primary outcome was the number of alive ICU-free days at Day 28. Secondary outcomes were 90-day survival, clinical cure 14 days post antibiotic cessation, alive organ failure-free days at Day 14, and duration of bacteremia. We enrolled 432 eligible participants with a median age of 64 years and an Acute Physiology and Chronic Health Evaluation II score of 20. There was no difference in ICU-free days: 18 days (interquartile range, 2-24) and 20 days (interquartile range, 3-24) in the continuous and intermittent groups (P = 0.38). There was no difference in 90-day survival: 74.3% (156 of 210) and 72.5% (158 of 218); hazard ratio, 0.91 (95% confidence interval, 0.63-1.31; P = 0.61). Clinical cure was 52.4% (111 of 212) and 49.5% (109 of 220); odds ratio, 1.12 (95% confidence interval, 0.77-1.63; P = 0.56). There was no difference in organ failure-free days (6 d; P = 0.27) and duration of bacteremia (0 d; P = 0.24). In critically ill patients with severe sepsis, there was no difference in outcomes between β-lactam antibiotic administration by continuous and intermittent infusion. Australian New Zealand Clinical Trials Registry number (ACT RN12612000138886).

  17. Regional block via continuous caudal infusion as sole anesthetic for inguinal hernia repair in conscious neonates.

    PubMed

    Mueller, Claudia M; Sinclair, Tiffany J; Stevens, Megan; Esquivel, Micaela; Gordon, Noah

    2017-03-01

    The use of general anesthesia in young children has come under increasing scrutiny due to its potential long-term neurotoxic effects. Meanwhile, regional anesthesia for surgical procedures in neonates has many advantages, including preservation of respiratory status and faster return to feeding. We describe the successful use of 3% 2-chloroprocaine administered via continuous caudal infusion as the sole anesthetic agent during elective surgical procedures in infants. A retrospective chart review of all patients who underwent elective surgical procedures under continuous caudal regional anesthetic at a single institution was performed. Thirty patients (27 males, three females) were identified: 28 patients underwent inguinal hernia repairs. Caudal anesthesia was established via continuous infusion of 3% 2-chloroprocaine through an indwelling catheter. Successful analgesia by regional block alone was achieved in all patients for the duration of each surgical procedure without need for rescue anesthesia. Mean operative time was 49 min. Patients were able to return to feeding immediately after surgery and were ready for discharge home within that day. Continuous caudal infusion of chloroprocaine is a safe and effective way to maintain adequate analgesia for elective surgeries in infants. This successful regional approach obviates the use of general anesthetic which reduces post-operative recovery time and avoids concerns for neurotoxicity.

  18. Continuous versus intermittent infusions of antibiotics for the treatment of severe acute infections.

    PubMed

    Shiu, Jennifer; Wang, Erica; Tejani, Aaron M; Wasdell, Michael

    2013-03-28

    Intravenous broad-spectrum antibiotics are indicated for the treatment of severe infections. However, the emergence of infections caused by multi-drug resistant organisms in conjunction with a lack of novel antibiotics has prompted the investigation of alternative dosing strategies to improve clinical efficacy and tolerability. To optimise pharmacokinetic and pharmacodynamic antibiotic parameters, continuous antibiotic infusions have been compared to traditional intermittent antibiotic infusions. To compare the clinical efficacy and safety of continuous intravenous administration of concentration-dependent and time-dependent antibiotics to traditional intermittent intravenous administration in adults with severe acute bacterial infections. The following electronic databases were searched in September 2012: The Cochrane Injuries Group Specialised Register, Cochrane Central Register of Controlled Trials (The Cochrane Library), MEDLINE (OvidSP), EMBASE (OvidSP), CINAHL, ISI Web of Science: Science Citation Index Expanded (SCI-EXPANDED), ISI Web of Science: Conference Proceedings Citation Index-Science (CPCI-S). The reference lists of all relevant material, the Internet and the trials registry www.clinicaltrials.gov for completed and ongoing trials were also searched. Randomized controlled trials in adults with a bacterial infection requiring intravenous antibiotic therapy comparing continuous versus intermittent infusions of antibiotics were included. Both time-dependent and concentration-dependent antibiotics were considered. Three independent authors performed data extraction for the included studies. All data was cross-checked and disagreements resolved by consensus. An intention to treat analysis was conducted using a random-effects model. Twenty-nine studies met inclusion criteria with a combined total of over 1,600 patients. The majority of included studies were judged to be at unclear or high risk of bias with regard to randomisation sequence generation

  19. Continuous versus bolus intermittent loop diuretic infusion in acutely decompensated heart failure: a prospective randomized trial

    PubMed Central

    2014-01-01

    Introduction Intravenous loop diuretics are a cornerstone of therapy in acutely decompensated heart failure (ADHF). We sought to determine if there are any differences in clinical outcomes between intravenous bolus and continuous infusion of loop diuretics. Methods Subjects with ADHF within 12 hours of hospital admission were randomly assigned to continuous infusion or twice daily bolus therapy with furosemide. There were three co-primary endpoints assessed from admission to discharge: the mean paired changes in serum creatinine, estimated glomerular filtration rate (eGFR), and reduction in B-type natriuretic peptide (BNP). Secondary endpoints included the rate of acute kidney injury (AKI), change in body weight and six months follow-up evaluation after discharge. Results A total of 43 received a continuous infusion and 39 were assigned to bolus treatment. At discharge, the mean change in serum creatinine was higher (+0.8 ± 0.4 versus -0.8 ± 0.3 mg/dl P <0.01), and eGFR was lower (-9 ± 7 versus +5 ± 6 ml/min/1.73 m2P <0.05) in the continuous arm. There was no significant difference in the degree of weight loss (-4.1 ± 1.9 versus -3.5 ± 2.4 kg P = 0.23). The continuous infusion arm had a greater reduction in BNP over the hospital course, (-576 ± 655 versus -181 ± 527 pg/ml P = 0.02). The rates of AKI were comparable (22% and 15% P = 0.3) between the two groups. There was more frequent use of hypertonic saline solutions for hyponatremia (33% versus 18% P <0.01), intravenous dopamine infusions (35% versus 23% P = 0.02), and the hospital length of stay was longer in the continuous infusion group (14. 3 ± 5 versus 11.5 ± 4 days, P <0.03). At 6 months there were higher rates of re-admission or death in the continuous infusion group, 58% versus 23%, (P = 0.001) and this mode of treatment independently associated with this outcome after adjusting for baseline and intermediate variables (adjusted

  20. Postoperative seroma formation after abdominoplasty with placement of continuous infusion local anesthetic pain pump

    PubMed Central

    Smith, Melissa M; Lin, Michael P; Hovsepian, Raffi V; Wood, David; Nguyen, Trung; Evans, Gregory RD; Wirth, Garrett A

    2009-01-01

    The most common complication after abdominoplasty is seroma formation. The incidence of seroma formation in abdominal procedures as a whole, including abdominoplasty, panniculectomy and transverse rectus abdominis myocutaneous flap abdominal donor sites, ranges from 1% to 38%. A recent concern among surgeons is the possibility of a causal relationship between the use of continuous infusion devices such as local anesthetic pain pumps and the development of seromas. A case of postoperative, persistent, recurrent seroma formation after abdominoplasty with the use of continuous infusion local anesthetic pain pump is presented. After several attempts at aspiration and drain catheter placement, only open surgical excision of the seroma cavity was found to be definitively effective in treating the development of seroma. PMID:21119843

  1. Cyclic ethanol metabolism in hypophysectomized rats continuously infused alcohol-containing diets

    USDA-ARS?s Scientific Manuscript database

    Chronic ethanol (EtOH) intake induces hepatic alcohol dehydrogenase (ADH) expression via disruption of insulin signaling in liver (JBC 2006; 281:1126-34). Total enteral nutrition (TEN) is a method of slow and continuous (approx. 23/day) feeding patients through an intragastric tube. Rats fed EtOH-co...

  2. Nutrient infusion bypassing duodenum-jejunum improves insulin sensitivity in glucose-tolerant and diabetic obese subjects.

    PubMed

    Salinari, Serenella; Carr, Richard D; Guidone, Caterina; Bertuzzi, Alessandro; Cercone, Stefania; Riccioni, Maria E; Manto, Andrea; Ghirlanda, Giovanni; Mingrone, Geltrude

    2013-07-01

    The mechanisms of type 2 diabetes remission after bariatric surgery is still not fully elucidated. In the present study, we tried to simulate the Roux-en-Y gastric bypass with a canonical or longer biliary limb by infusing a liquid formula diet into different intestinal sections. Nutrients (Nutrison Energy) were infused into mid- or proximal jejunum and duodenum during three successive days in 10 diabetic and 10 normal glucose-tolerant subjects. Plasma glucose, insulin, C-peptide, glucagon, incretins, and nonesterified fatty acids (NEFA) were measured before and up to 360 min following. Glucose rate of appearance (Ra) and insulin sensitivity (SI), secretion rate (ISR), and clearance were assessed by mathematical models. SI increased when nutrients were delivered in mid-jejunum vs. duodenum (SI × 10⁴ min⁻¹·pM⁻¹: 1.11 ± 0.44 vs. 0.62 ± 0.22, P < 0.015, in controls and 0.79 ± 0.34 vs. 0.40 ± 0.20, P < 0.05, in diabetic subjects), whereas glucose Ra was not affected. In controls, Sensitivity of NEFA production was doubled in mid-jejunum vs. duodenum (2.80 ± 1.36 vs. 1.13 ± 0.78 × 10⁶, P < 0.005) and insulin clearance increased in mid-jejunum vs. duodenum (2.05 ± 1.05 vs. 1.09 ± 0.38 l/min, P < 0.03). Bypass of duodenum and proximal jejunum by nutrients enhances insulin sensitivity, inhibits lipolysis, and increases insulin clearance. These results may further our knowledge of the effects of bariatric surgery on both insulin resistance and diabetes.

  3. Continuously Infusing Hyperpolarized 129Xe into Flowing Aqueous Solutions Using Hydrophobic Gas Exchange Membranes

    PubMed Central

    Cleveland, Zackary I.; Möller, Harald E.; Hedlund, Laurence W.; Driehuys, Bastiaan

    2009-01-01

    Hyperpolarized (HP) 129Xe yields high signal intensities in magnetic resonance (MR) and, through its large chemical shift range of ∼300 ppm, provides detailed information about the local chemical environment. To exploit these properties in aqueous solutions and living tissues requires the development of methods for efficiently dissolving HP 129Xe over an extended time period. To this end, we have used commercially available gas exchange modules to continuously infuse concentrated HP 129Xe into flowing liquids, including rat whole blood, for periods as long as one hour, and have demonstrated the feasibility of dissolved-phase MR imaging with sub-millimeter resolution within minutes. These modules, which exchange gases using hydrophobic microporous polymer membranes, are compatible with a variety of liquids and are suitable for infusing HP 129Xe into the bloodstream in vivo. Additionally, we have developed a detailed mathematical model of the infused HP 129Xe signal dynamics that should be useful in designing improved infusion systems that yield even higher dissolved HP 129Xe signal intensities. PMID:19702286

  4. Insulin Infusion on Postoperative Complications of Coronary Artery Bypass Graft in Patients With Diabetes Mellitus

    PubMed Central

    Masoumi, Gholamreza; Frasatkhish, Rasoul; Bigdelian, Hamid; Ziyaefard, Mohsen; Sadeghpour-Tabae, Ali; Mansouri, Mojtaba; Jalali, Alireza

    2014-01-01

    Background: Cardiovascular events are common in patients with diabetes mellitus (DM), which make coronary artery bypass graft (CABG) a highly demanded surgery in this population. Tight control of blood glucose in patients with DM is beneficial in reducing postoperative complications; however, the adequate range has not been determined yet. Objectives: This study aimed to investigate the effect of semi-tight (moderate) control of DM on complications and serum glucose levels during and after CABG. Patients and Methods: In this prospective clinical trial, 18 and 31 patients with and without DM, respectively, who were referred to Shahid Chamran Hospital, Isfahan, Iran, for elective CABG surgery, were enrolled. For DM group, patients with controlled DM (i.e. glycosylated hemoglobin levels [HgA1C] ≤ 7%) were recruited. Blood glucose level (blood sugar, BS) was measured after anesthesia, during pumping, warming, off pumping, six and 12 hours after Intensive Care Unit (ICU) admission, and at discharging from the hospital. The hemodynamic state of the patients, bleeding, need of blood transfusion, infection, and duration of hospitalization were also monitored and recorded. Results: None of the BS measurements (FBS, after anesthesia, on-pump, warming, off pump, six and 12 hours after ICU admission, and at discharge) were significantly different between study groups (P > 0.05). Frequency of surgery site bleeding and blood transfusion need were not significantly different between these groups (P > 0.05). Conclusions: Semi-tight control of DM with insulin infusion during operation did not led to any difference in the type and rate of CABG complications between patients with well-controlled and those without DM; however, BS levels in patients with well-controlled DM could be more easily controlled. PMID:25478540

  5. Continuous infusion of amphotericin B: preliminary experience at Faculdade de Medicina da Fundação ABC.

    PubMed

    Uehara, Roberto Palermo; Sá, Victor Hugo Lara de; Koshimura, Erika Tae; Prudente, Fernanda Vilas Boas; Tucunduva, Luciana Tomanik Cardozo de Mello; Gonçalves, Marina Sahade; Samano, Eliana Sueco Tibana; del Giglio, Auro

    2005-09-01

    Intravenous amphotericin B deoxycholate (AmB-D) infusions, usually given over 4 hours, frequently induce nephrotoxicity and undesirable infusion-related side effects such as rigors and chills. There is evidence in the literature that the use of AmB-D in the form of continuous 24-hour infusion is less toxic than the usual four-hour infusion of this drug. Our objective was to evaluate the efficacy and safety of continuous infusion of AmB-D for the treatment of persistent fever in neutropenic patients with hematological malignancies after chemotherapy. Observational retrospective analysis of our experience with continuous infusion of AmB-D, at Faculdade de Medicina da Fundação ABC and Hospital Estadual Mário Covas in Santo André. From October 2003 to May 2004, 12 patients with hematological malignancies and chemotherapy-induced neutropenia received 13 cycles of continuous infusion of AmB-D. The median dose of AmB-D was 0.84 mg/kg/day (0.33 to 2.30 mg/kg/day). Concomitant use of nephrotoxic medications occurred in 92% of the cycles. Nephrotoxicity occurred in 30.76% of the cycles, hypokalemia in 16.67%, hepatotoxicity in 30% and adverse infusion-related events in 23%. All patients survived for at least seven days after starting continuous infusion of AmB-D, and clinical resolution occurred in 76% of the cycles. Continuous infusion of AmB-D can be used in our Institution as an alternative to the more toxic four-hour infusion of AmB-D and possibly also as an alternative to the more expensive liposomal formulations of the drug.

  6. Use of continuous subcutaneous anesthetic infusion in cardiac surgical patients after median sternotomy.

    PubMed

    Koukis, Ioannis; Argiriou, Mihalis; Dimakopoulou, Antonia; Panagiotakopoulos, Victor; Theakos, Nikolaos; Charitos, Christos

    2008-01-25

    The use of opioid analgesics to control pain after median sternotomy in cardiac surgical patients is worldwide accepted and established. However, opioids have a wide range of possible side effects, concerning prolonged extubation time, gastrointestinal tract dyskinesia and urinary tract disorders mostly retention. All these may lead to a prolonged ICU stay or overall hospitalization time increase. To determine whether a continuous subcutaneous regional anesthetic infusion delivered directly to the sternotomy site would result in decreased levels of postoperative pain and opioid requirements in cardiac surgical patients undergoing median sternotomy. The continuous subcutaneous infusion (OnQ Painbuster system) was applied in 37 patients. 3 patients were exempted due to prolonged ICU stay. 29 patients underwent CABG, 5 had AVR, 1 MVR and modified Maze, 1 patient had a 3-valve repair due to endocarditis and another one had reconstruction of the left ventricle. Requirements of opioid analgesics were recorded for 96 hours after operation. Pain was assessed using the visual analog scale and the total postoperative hospital length of stay was also measured. The postoperative pain was significantly diminished (0 - 3 at VAS). The mean postoperative length of stay was 5,8 days, rather improved compared to the average stay of 6,7 days. Continuous subcutaneous infusion of ropivacaine directly at the median sternotomy significantly diminishes postoperative pain and the need for opioid analgesic use. Moreover, it seems to reduce overall postoperative length of stay for all cardiac surgical patients.

  7. Use of continuous subcutaneous anesthetic infusion in cardiac surgical patients after median sternotomy

    PubMed Central

    Koukis, Ioannis; Argiriou, Mihalis; Dimakopoulou, Antonia; Panagiotakopoulos, Victor; Theakos, Nikolaos; Charitos, Christos

    2008-01-01

    The use of opioid analgesics to control pain after median sternotomy in cardiac surgical patients is worldwide accepted and established. However, opioids have a wide range of possible side effects, concerning prolonged extubation time, gastrointestinal tract dyskinesia and urinary tract disorders mostly retention. All these may lead to a prolonged ICU stay or overall hospitalization time increase. To determine whether a continuous subcutaneous regional anesthetic infusion delivered directly to the sternotomy site would result in decreased levels of postoperative pain and opioid requirements in cardiac surgical patients undergoing median sternotomy. The continuous subcutaneous infusion (OnQ Painbuster system) was applied in 37 patients. 3 patients were exempted due to prolonged ICU stay. 29 patients underwent CABG, 5 had AVR, 1 MVR and modified Maze, 1 patient had a 3-valve repair due to endocarditis and another one had reconstruction of the left ventricle. Requirements of opioid analgesics were recorded for 96 hours after operation. Pain was assessed using the visual analog scale and the total postoperative hospital length of stay was also measured. The postoperative pain was significantly diminished (0 – 3 at VAS). The mean postoperative length of stay was 5,8 days, rather improved compared to the average stay of 6,7 days. Continuous subcutaneous infusion of ropivacaine directly at the median sternotomy significantly diminishes postoperative pain and the need for opioid analgesic use. Moreover, it seems to reduce overall postoperative length of stay for all cardiac surgical patients. PMID:18221527

  8. Population pharmacokinetics of meropenem during continuous infusion in surgical ICU patients.

    PubMed

    Kees, Martin G; Minichmayr, Iris K; Moritz, Stefan; Beck, Stefanie; Wicha, Sebastian G; Kees, Frieder; Kloft, Charlotte; Steinke, Thomas

    2016-03-01

    Continuous infusion of meropenem is a candidate strategy for optimization of its pharmacokinetic/pharmacodynamic profile. However, plasma concentrations are difficult to predict in critically ill patients. Steady-state concentrations of meropenem were determined prospectively during continuous infusion in 32 surgical ICU patients (aged 21-85 years, body weight 55-125 kg, APACHE II 5-29, measured creatinine clearance 22.7-297 mL/min). Urine was collected for the quantification of renal clearance of meropenem and creatinine. Cystatin C was measured as an additional marker of renal function. Population pharmacokinetic models were developed using NONMEM(®) , which described total meropenem clearance and its relationship with several estimates of renal function (measured creatinine clearance CLCR , Cockcroft-Gault formula CLCG , Hoek formula, 1/plasma creatinine, 1/plasma cystatin C) and other patient characteristics. Any estimate of renal function improved the model performance. The strongest association of clearance was found with CLCR (typical clearance = 11.3 L/h × [1 + 0.00932 × (CLCR  - 80 mL/min)]), followed by 1/plasma cystatin C; CLCG was the least predictive covariate. Neither age, weight, nor sex was found to be significant. These models can be used to predict dosing requirements or meropenem concentrations during continuous infusion. The covariate CLCR offers the best predictive performance; if not available, cystatin C may provide a promising alternative to plasma creatinine.

  9. [Continuous infusion versus bolus injection of loop diuretics in acute heart failure: a literature review].

    PubMed

    Leto, Laura; Aspromonte, Nadia; Feola, Mauro

    2012-04-01

    Intravenous loop diuretics are increasingly used to treat symptoms and signs of fluid overload in acute heart failure, a clinical condition associated with high morbidity and mortality rates. Although diuretic therapy is widely used and strongly recommended by most recent clinical guidelines, prospective studies and randomized clinical trials are lacking and hence there is no reliable evidence regarding the best therapy in terms of doses, ways and methods of administration. With heart failure progression, the efficacy of loop diuretics is impaired by diuretic resistance characterized by a decreased diuretic and natriuretic effect of drugs. This review focuses on the current management of acute heart failure with diuretic therapy. Continuous diuretic infusion seems to be a good choice, from a pharmacokinetic point of view, when fluid overload is refractory to conventional therapy. Several available studies comparing bolus injection to continuous infusion of loop diuretics proved the latter to be an effective and safe method of administration. Continuous infusion seems to produce a constant plasma drug concentration with a more uniform daily diuretic and natriuretic effect and a greater safety profile (fewer adverse events such as worsening renal failure, electrolyte imbalance, ototoxicity). In addition, the analysis of available literature data did not provide conclusive evidence about the effects on clinical outcomes (mortality, rehospitalization rates, adverse events).

  10. Clinical cure of ventilator-associated pneumonia treated with piperacillin/tazobactam administered by continuous or intermittent infusion.

    PubMed

    Lorente, Leonardo; Jiménez, Alejandro; Martín, María M; Iribarren, José Luis; Jiménez, Juan José; Mora, María L

    2009-05-01

    The standard mode of administration of piperacillin treatment is by intermittent infusion. However, continuous infusion may be advantageous as beta-lactam antibiotics exhibit time-dependent antibacterial activity. In previous studies, we found a higher rate of clinical cure of ventilator-associated pneumonia (VAP) by continuous infusion rather than intermittent infusion of meropenem and ceftazidime. Therefore, the objective of this historical cohort study was to establish the clinical efficacy of piperacillin/tazobactam (PIP/TAZ) administered by continuous and intermittent infusion in the treatment of VAP in patients without renal failure. Logistic regression analysis showed a higher probability of clinical cure of VAP by continuous compared with intermittent infusion when the microorganism responsible for VAP had a minimum inhibitory concentration (MIC) of 8 microg/mL [8/9 (88.9%) vs. 6/15 (40.0%); odds ratio (OR)=10.79, 95% confidence interval (CI) 1.01-588.24; P=0.049] or 16 microg/mL [7/8 (87.5%) vs. 1/6 (16.7%); OR=22.89, 95% CI 1.19-1880.78; P=0.03]. Thus, administration of PIP/TAZ by continuous infusion may be considered more effective than intermittent infusion for the treatment of VAP caused by Gram-negative bacteria when the MIC of the microorganism responsible for VAP is 8-16 microg/mL in patients without renal failure.

  11. Type of homogenization and fat loss during continuous infusion of human milk.

    PubMed

    García-Lara, Nadia Raquel; Escuder-Vieco, Diana; Alonso Díaz, Clara; Vázquez Román, Sara; De la Cruz-Bértolo, Javier; Pallás-Alonso, Carmen Rosa

    2014-11-01

    Substantial fat loss may occur during continuous feeding of human milk (HM). A decrease of fat loss has been described following homogenization. Well-established methods of homogenization of HM for routine use in the neonatal intensive care unit (NICU) would be desirable. We compared the loss of fat based on the use of 3 different methods for homogenizing thawed HM during continuous feeding. Sixteen frozen donor HM samples were thawed, homogenized with ultrasound and separated into 3 aliquots ("baseline agitation," "hourly agitation," and "ultrasound"), and then frozen for 48 hours. Aliquots were thawed again and a baseline agitation was applied. Subsequently, aliquots baseline agitation and hourly agitation were drawn into a syringe, while ultrasound was applied to aliquot ultrasound before it was drawn into a syringe. The syringes were loaded into a pump (2 mL/h; 4 hours). At hourly intervals the hourly agitation infusion was stopped, the syringe was disconnected and gently shaken. During infusion, samples from the 3 groups were collected hourly for analysis of fat and caloric content. The 3 groups of homogenization showed similar fat content at the beginning of the infusion. For fat, mean (SD) hourly changes of -0.03 (0.01), -0.09 (0.01), and -0.09 (0.01) g/dL were observed for the hourly agitation, baseline agitation, and ultrasound groups, respectively. The decrease was smaller for the hourly agitation group (P < .001). When thawed HM is continuously infused, a smaller fat loss is observed when syringes are agitated hourly versus when ultrasound or a baseline homogenization is used. © The Author(s) 2014.

  12. Continuous infusion or bolus injection of loop diuretics for congestive heart failure?

    PubMed

    Zepeda, Patricio; Rain, Carmen; Sepúlveda, Paola

    2016-04-22

    Loop diuretics are widely used in acute heart failure. However, there is controversy about the superiority of continuous infusion over bolus administration. Searching in Epistemonikos database, which is maintained by screening 30 databases, we identified four systematic reviews including 11 pertinent randomized controlled trials overall. We combined the evidence using meta-analysis and generated a summary of findings following the GRADE approach. We concluded continuous administration of loop diuretics probably reduces mortality and length of stay compared to intermittent administration in patients with acute heart failure.

  13. Infective endocarditis caused by Enterococcus faecalis treated with continuous infusion of ampicillin without adjunctive aminoglycosides.

    PubMed

    Ogawa, Taku; Sato, Masatoshi; Yonekawa, Shinsuke; Nakagawa, Chiyo; Uno, Kenji; Kasahara, Kei; Maeda, Koichi; Konishi, Mitsuru; Mikasa, Keiichi

    2013-01-01

    Aminoglycosides are useful antimicrobial agents for treating infective endocarditis; however, they occasionally cause troublesome side effects, such as nephrotoxicity and ototoxicity. We herein report a case of infective endocarditis caused by Enterococcus faecalis that was treated successfully with continuous infusion of ampicillin without adjunctive aminoglycosides. The serum ampicillin concentrations were higher than the minimal inhibitory concentration for the target strain. Although the use of ampicillin monotherapy is currently avoided because double β-lactam therapy is reportedly more effective, continuous penicillin administration remains an effective therapeutic choice for treating infective endocarditis.

  14. Review of Continuous Infusion Neuromuscular Blocking Agents in the Adult Intensive Care Unit.

    PubMed

    Smetana, Keaton S; Roe, Neil A; Doepker, Bruce A; Jones, G Morgan

    The use of continuous infusion neuromuscular blocking agents remains controversial. The clinical benefit of these medications may be overshadowed by concerns of propagating intensive care unit-acquired weakness, which may prolong mechanical ventilation and impair the inability to assess neurologic function or pain. Despite these risks, the use of neuromuscular blocking agents in the intensive care unit is indicated in numerous clinical situations. Understanding pharmacologic nuances and clinical roles of these agents will aid in facilitating safe use in a variety of acute disease processes. This article provides clinicians with information regarding pharmacologic differences, indication for use, adverse effects, recommended doses, ancillary care, and monitoring among agents used for continuous neuromuscular blockade.

  15. Continuous versus intermittent infusion of vancomycin in adult patients: A systematic review and meta-analysis.

    PubMed

    Hao, Jing-Jing; Chen, Han; Zhou, Jian-Xin

    2016-01-01

    Continuous infusion of vancomycin (CIV) and intermittent infusion of vancomycin (IIV) are two major administration strategies in clinical settings. However, previous articles comparing the efficacy and safety of CIV versus IIV showed inconsistent results. Therefore, a meta-analysis was conducted to compare the efficacy and safety of CIV and IIV. PubMed, the Cochrane Library and Web of Science up to June 2015 were searched using the keywords 'vancomycin', 'intravenous', 'parenteral', 'continuous', 'intermittent', 'discontinuous', 'infusion', 'administration' and 'dosing'. Eleven studies were included in the meta-analysis. Neither heterogeneity nor publication bias were observed. Patients treated with CIV had a significantly lower incidence of nephrotoxicity compared with patients receiving IIV [risk ratio (RR)=0.61, 95% confidence interval (CI) 0.47-0.80; P<0.001]. No significant difference in treatment failure between the two groups was detected. Mortality between patients receiving CIV and patients receiving IIV was similar (RR=1.15, 95% CI 0.85-1.54; P=0.365). This meta-analysis showed that CIV had superior safety compared with IIV, whilst the clinical efficacy was not significantly different. A further multicentre, randomised controlled trial is required to confirm these results.

  16. Effect of Continuous Propofol Infusion in Rat on Tau Phosphorylation with or without Temperature Control.

    PubMed

    Huang, Chunxia; Ng, Olivia Tsz-Wa; Ho, Yuen-Shan; Irwin, Michael Garnet; Chang, Raymond Chuen-Chung; Wong, Gordon Tin-Chun

    2016-01-01

    Several studies suggest a relationship between anesthesia-induced tau hyperphosphorylation and the development of postoperative cognitive dysfunction. This study further characterized the effects of continuous propofol infusion on tau protein phosphorylation in rats, with or without temperature control. Propofol was administered intravenously to 8-10-week-old male Sprague-Dawley rats and infused to the loss of the righting reflex for 2 h continuously. Proteins from cortex and hippocampus were examined by western blot and immunohistochemistry. Rectal temperature was significantly decreased during propofol infusion. Propofol with hypothermia significantly increased phosphorylation of tau at AT8, AT180, Thr205, and Ser199 in cortex and hippocampus except Ser396. With temperature maintenance, propofol still induced significant elevation of AT8, Thr205, and Ser199 in cortex and hippocampus; however, increase of AT180 and Ser396 was only found in hippocampus and cortex, respectively. Differential effects of propofol with or without hypothermia on multiple tau related kinases, such as Akt/GSK3β, MAPK pathways, or phosphatase (PP2A), were demonstrated in region-specific manner. These findings indicated that propofol increased tau phosphorylation under both normothermic and hypothermic conditions, and temperature control could partially attenuate the hyperphosphorylation of tau. Further studies are warranted to determine the long-term impact of propofol on the tau pathology and cognitive functions.

  17. Pilot study of interaction of radiation therapy with doxorubicin by continuous infusion

    SciTech Connect

    Rosenthal, C.J.; Rotman, M.

    1988-01-01

    Doxorubicin was initially administered alone by continuous infusion for 5 days every 3 weeks in escalating doses to 13 patients with advanced metastatic and/or recurrent malignancies. The maximum tolerable dosage was 13 mg/m2 per day for 5 days. Kinetic data showed a steady level of 60 ng/ml for 4 days and a biphasic disappearance curve. Radiation therapy (150-200 cGy per session) was then administered in 5-day cycles, every 3 weeks, concomitantly with continuous infusion of doxorubicin (12 mg/m2 per day) to 21 patients with various advanced unresectable recurrent or metastatic malignancies. Four of 9 patients with soft tissue sarcomas achieved complete response after a radiation dose of 2,206 +/- 590 (SD) cGy and 3 had partial response; the median durations of the response were 142 +/- 65 (SD) weeks for complete response and 28 +/- 10 weeks for partial response. Of 4 patients with primary hepatoma, 2 achieved partial response after 1,290 +/- 210 cGy. No response was seen in any of the 7 patients with adenocarcinoma of the gastrointestinal tract or breast. Complications of this regimen included moderate leukopenia and thrombocytopenia, mucositis, skin erythema, and decrease of the ventricular ejection fraction at a cumulative doxorubicin dose of 840 mg/m2. We conclude that doxorubicin given by protracted infusion can be safely administered with concomitant radiation and appears to enhance the effects of radiation on most soft tissue sarcomas and on some hepatocellular carcinomas.

  18. The use of dexmedetomidine continuous rate infusion for horses undergoing transvenous electrical cardioversion — A case series

    PubMed Central

    Marly-Voquer, Charlotte; Schwarzwald, Colin C.; Bettschart-Wolfensberger, Regula

    2016-01-01

    Five horses were presented for treatment of atrial fibrillation by transvenous electrical cardioversion (TVEC). A dexmedetomidine infusion was administered for sedation during positioning of the cardioversion catheters, and continued during general anesthesia. Shocks were applied until return to sinus rhythm. Dexmedetomidine infusion provided excellent conditions for TVEC catheter placement and procedure. PMID:26740702

  19. A Novel Technique for Split-Thickness Skin Donor Site Pain Control: Subcutaneous Catheters for Continuous Local Anesthetic Infusion

    DTIC Science & Technology

    2012-01-01

    catheters are primed with 2 ml of 1⁄4% bupivacaine and attached to the ON-Q Pain Pump device, which infuses at a rate of 4 ml/hr. The use of either 0.2...ropivacaine or 1⁄4% bupivacaine for continuous infusion has been de- scribed; but due to the bacteriostatic properties of the latter, this is the

  20. Dodecanedioic acid infusion induces a sparing effect on whole-body glucose uptake, mainly in non-insulin-dependent diabetes mellitus.

    PubMed

    Mingrone, G; De Gaetano, A; Greco, A V; Capristo, E; Benedetti, G; Castagneto, M; Gasbarrini, G

    1997-11-01

    Even-numbered dicarboxylic acids (DA) have been proposed as an alternative fuel substrate in parenteral nutrition. In particular, dodecanedioic acid (C12) shows a rapid plasma clearance from tissues, a very low urinary excretion compared with other DA and a high oxidation rate. The aim of the present study was to investigate the effect of C12 infusion on insulin-stimulated glucose uptake in patients with non-insulin-dependent diabetes mellitus (NIDDM) compared with healthy volunteers. A primed-constant infusion of C12 (0.39 mmol/min) was administered over 240 min, and at 120 min a 2 h euglycaemic hyperinsulinaemic clamp was performed. Blood specimens were sampled every 30 min and fractioned urines were collected over 24 h. The levels of C12 were measured by HPLC. Indirect calorimetry was performed continuously during the entire session. Body composition was assessed in all subjects studied to obtain fat-free mass (FFM) values. Whole-body glucose uptake decreased significantly during C12 infusion in both groups, although this effect was much more evident (P < 0.01) in NIDDM patients (52.4 (SD 15.8) % decrease compared with saline) than in controls (25.9 (SD 12.1) % decrease). The M value (mumol/kgFFM per min) was reduced by C12 to lower levels in NIDDM patients than in normal controls (12.6 (SD 3.9) v. 25.9 (SD 4.5), P < 0.01). Urinary excretion of C12 over 24 h was significantly lower in NIDDM patients than in controls (4.26 (SD 0.30) mmol v. 5.43 (SD 0.48), P < 0.01), corresponding to less than 3% of the administered dose. The infusion of C12 decreased non-protein RQ significantly in both groups of patients. In conclusion, this study shows, for the first time, that C12 significantly reduces glucose uptake in both normal controls and NIDDM patients, although this sparing effect on glucose uptake is much more pronounced in diabetic patients. These data suggest that C12 decreases glucose uptake and oxidation, mainly through a mechanism of substrate competition. Thus

  1. Severe methemoglobinemia caused by continuous lidocaine infusion in a term neonate.

    PubMed

    Bohnhorst, Bettina; Hartmann, Hans; Lange, Matthias

    2016-12-28

    Neonates and young infants are especially prone to develop drug-induced methemoglobinemia. Therefore, lidocaine is not licensed as local anesthetic in children below the age of 3 months. However, its systemic use is advocated for neonatal seizures. Cardiac arrhythmia has been reported as sole major side effect. Here we report a case of severe methemoglobinemia caused by continuous infusion of lidocaine in a term neonate with neonatal seizures. The increase of methemoglobin up to 13.8% was accompanied by hypoxemia and cyanosis, necessitating additional inspired oxygen and CPAP ventilation. After stopping lidocaine infusion methemoglobin levels fell and the neonate could be weaned from ventilation. Neonates treated with lidocaine for seizures must be monitored for the occurrence of methemoglobinemia.

  2. The effect of intravenous insulin infusion on renal blood flow in conscious sheep is partially mediated by nitric oxide but not by prostaglandins.

    PubMed

    Tebot, I; Bonnet, J-M; Paquet, C; Ayoub, J-Y; Da Silva, S M; Louzier, V; Cirio, A

    2012-04-01

    To test the effect of insulin on renal perfusion and the participation of NO and PG as mediators of this response, renal blood flow (RBF) was measured in sheep (n = 8) implanted with ultrasonic flow probes around renal arteries and with a systemic arterial pressure (SAP, n = 4) telemetry device. Three protocols were performed: 1) RBF and SAP were recorded (0800 to 1800 h) in fed and fasted sheep, with the latter receiving intravenous (i.v.) infusions (0.5 mL/min) of insulin at 2 or 6 mU/(kg·min); 2) fasted sheep received i.v. infusions of either an inhibitor of NO synthesis (N(G)-nitro-L-arginine methyl ester, L-NAME) alone [0.22 mg/(kg·min), 1000 to 1200 h] or L-NAME (1000 to 1200 h) + insulin during the second hour (6 mU/(kg·min), 1100 to 1200 h); and 3) the same protocol was followed as in protocol 2, substituting L-NAME with ketoprofen [0.2 mg/(kg·min)], a cyclooxygenase inhibitor. In all protocols, plasma insulin and glucose were determined. During insulin administration, euglycemia was maintained and hypokalemia was prevented by infusing glucose and KCl solutions. After the onset of meals, a long-lasting 18% increase in RBF and a 48% insulin increase were observed (P < 0.05), without changes in SAP. Low- and high-dose insulin infusions increased RBF by 19 and 40%, respectively (P < 0.05). As after meals, the increases in RBF lasted longer than the insulin increase (P < 0.05). The L-NAME infusion decreased RBF by 15% (P < 0.05); when insulin was added, RBF increased to preinfusion values. Ketoprofen decreased RBF by 9% (P < 0.05); when insulin was added, RBF increased to 13% above preinfusion values (P < 0.05). In no case was a modification in SAP or glucose noted during the RBF changes. In conclusion, insulin infusion mimics the meal-dependent increase in RBF, independent of SAP, and lasts longer than the blood insulin plateau. The RBF increase induced by insulin was only partially prevented by L-NAME. Ketoprofen failed to prevent the insulin

  3. Adrenocortical suppression and recovery after continuous hypnotic infusion: etomidate versus its soft analogue cyclopropyl-methoxycarbonyl metomidate.

    PubMed

    Ge, Rile; Pejo, Ervin; Cotten, Joseph F; Raines, Douglas E

    2013-01-30

    Etomidate is no longer administered as a continuous infusion for anesthetic maintenance or sedation, because it results in profound and persistent suppression of adrenocortical steroid synthesis with potentially lethal consequences in critically ill patients. We hypothesized that rapidly metabolized soft analogues of etomidate could be developed that do not produce persistent adrenocortical dysfunction even after prolonged continuous infusion. We hope that such agents might also provide more rapid and predictable anesthetic emergence. We have developed the soft etomidate analogue cyclopropyl-methoxycarbonyl etomidate (CPMM). Upon termination of 120-minute continuous infusions, hypnotic and encephalographic recoveries occur in four minutes. The aims of this study were to assess adrenocortical function during and following 120-minute continuous infusion of CPMM and to compare the results with those obtained using etomidate. Dexamethasone-suppressed rats were randomized into an etomidate group, CPMM group, or control group. Rats in the etomidate and CPMM groups received 120-minute continuous infusions of etomidate and CPMM, respectively. Rats in the control group received neither hypnotic. In the first study, adrenocortical function during hypnotic infusion was assessed by administering adrenocorticotropic hormone (ACTH) 90 minutes after the start of the hypnotic infusion and measuring plasma corticosterone concentrations at the end of the infusion 30 minutes later. In the second study, adrenocortical recovery following hypnotic infusion was assessed by administering ACTH every 30 minutes after infusion termination and measuring plasma corticosterone concentrations 30 minutes after each ACTH dose. During hypnotic infusion, ACTH-stimulated serum corticosterone concentrations were significantly lower in the CPMM and etomidate groups than in the control group (100 ± 64 ng/ml and 33 ± 32 ng/ml versus 615 ± 265 ng/ml, respectively). After hypnotic infusion, ACTH

  4. Pharmacokinetics of continuous-infusion meropenem in a pediatric patient receiving extracorporeal life support.

    PubMed

    Cies, Jeffrey J; Moore, Wayne S; Dickerman, Mindy J; Small, Christine; Carella, Dominick; Chopra, Arun; Parker, Jason

    2014-10-01

    Meropenem, a broad-spectrum carbapenem, is commonly used for empirical and definitive therapy in the pediatric intensive care unit (ICU). Pharmacokinetic data to guide dosing in children, however, are limited to healthy volunteers or patients who are not in the ICU. Adult data demonstrate that pharmacokinetic parameters such as the volume of distribution and clearance can be significantly altered in individuals receiving extracorporeal membrane oxygenation (ECMO). Alterations in the volume of distribution and clearance of antimicrobials in patients with sepsis and septic shock have also been documented, and these patients have demonstrated lower than expected antimicrobial serum concentrations based on standard dosing regimens. Therefore, an understanding of the pharmacokinetic changes in critically ill children receiving ECMO is crucial to determining the most appropriate dose and dosing interval selection for any antimicrobial therapy. In this case report, we describe the pharmacokinetics of a continuous infusion of meropenem in a pediatric cardiac ICU patient who was receiving concurrent extracorporeal life support. The patient was an 8-month-old male infant who underwent a Glenn procedure and pulmonary artery reconstruction. Postoperatively, he required ECMO with a total run of 21 days. On day 11 of ECMO, a bronchoalveolar lavage was performed, and blood cultures from days 11 and 12 of ECMO grew Pseudomonas aeruginosa, with a meropenem minimum inhibitory concentration (MIC) of 0.5 μg/ml. On ECMO day 13, meropenem was initiated with a loading dose of 40 mg/kg and infused over 30 minutes, followed by a continuous infusion of 200 mg/kg/day. A meropenem serum concentration measured 8 hours after the start of the infusion was 46 μg/ml. Repeat levels were measured on days 3 and 9 of meropenem therapy and were 39 and 42 μg/ml, respectively. Repeat blood and respiratory cultures remained negative. This meropenem regimen (40-mg/kg bolus followed by a

  5. Continuation versus discontinuation of oxytocin infusion during the active phase of labour: a randomised controlled trial.

    PubMed

    Bor, P; Ledertoug, S; Boie, S; Knoblauch, N O; Stornes, I

    2016-01-01

    To investigate whether discontinuation of oxytocin infusion increases the duration of the active phase of labour and reduces maternal and neonatal complications. Randomised controlled trial. Department of Obstetrics and Gynaecology, Regional Hospital of Randers, Denmark. Women with singleton pregnancy in the vertex position undergoing labour induction or augmentation. Two hundred women were randomised when cervical dilation was ≤4 cm to either continue or discontinue oxytocin infusion when cervical dilation reached 5 cm. The primary outcome was duration of the active phase of labour, defined as the time period from 5 cm of cervical dilation until delivery. Secondary outcomes were mode of delivery, uterine tachysystole, hyperstimulation, abnormalities in fetal heart rate, postpartum haemorrhage rate, perineal tears, and neonatal outcomes. The active phase of labour was longer by 41 minutes (95% confidence interval 11-75 minutes) in the discontinued group (median 125 minutes in 85 women who had reached the active phase and delivered vaginally) versus the continued group (median 88 minutes in 78 women). The incidence of fetal heart rate abnormalities (51 versus 20%) and uterine hyperstimulation (12 versus 2%) was significantly greater in the continued than the discontinued oxytocin group. The incidence of tachysystole, caesarean deliveries, postpartum haemorrhage, third degree perineal tears and adverse neonatal outcomes was higher in the continued group, but did not reach significance. Discontinuation of oxytocin infusion in the active phase of labour may improve some labour outcomes but has the disadvantage of increasing the duration of the active phase of labour. Stopping oxytocin in the active phase seems to make labour less complicated but lengthens duration. © 2015 Royal College of Obstetricians and Gynaecologists.

  6. A Mathematical Model for Comparison of Bolus Injection, Continuous Infusion, and Liposomal Delivery of Doxorubicin to Tumor Cells1

    PubMed Central

    El-Kareh, Ardith W; Secomb, Timothy W

    2000-01-01

    Abstract Determining the optimal mode of delivery for doxorubicin is important given the wide use of the drug against many tumor types. The relative performances of bolus injection, continuous infusion, liposomal and thermoliposomal delivery are not yet definitely established from clinical trials. Here, a mathematical model is used to compare bolus injection, continuous infusion for various durations, liposomal and thermoliposomal delivery of doxorubicin. Effects of the relatively slow rate, and saturability, of doxorubicin uptake by cells are included. Peak concentrations attained in tumor cells are predicted and used as a measure of antitumor effectiveness. To measure toxicity, plasma area under the curve (AUC) and peak plasma concentrations of free doxorubicin are computed. For continuous infusion, the duration of infusion significantly affects predicted outcome. The optimal infusion duration increases with dose, and is in the range 1 to 3 hours at typical doses. The simulations suggest that continuous infusion for optimal durations is superior to the other protocols. Nonthermosensitive liposomes approach the efficacy of continuous infusion only if they release drug at optimal rates. Predictions for thermosensitive liposomes indicate a potential advantage at some doses, but only if hyperthermia is applied locally so that the blood is not significantly heated. PMID:11005567

  7. Pharmacokinetic-pharmacodynamic evaluation of ceftazidime continuous infusion vs intermittent bolus injection in septicaemic melioidosis.

    PubMed

    Angus, B J; Smith, M D; Suputtamongkol, Y; Mattie, H; Walsh, A L; Wuthiekanun, V; Chaowagul, W; White, N J

    2000-08-01

    Experimental studies have suggested that constant intravenous infusion would be preferable to conventional intermittent bolus administration of beta-lactam antibiotics for serious Gram-negative infections. Severe melioidosis (Burkholderia pseudomallei infection) carries a mortality over 40% despite treatment with high dose ceftazidime. The aim of this study was to measure the pharmacokinetic and pharmacodynamic effects of continuous infusion of ceftazidime vs intermittent bolus dosing in septicaemic melioidosis. Patients with suspected septicaemic melioidosis were randomised to receive ceftazidime 40 mg kg(-1) 8 hourly by bolus injection or 4 mg kg(-1) h(-1) by constant infusion following a 12 mg kg(-1) priming dose and pharmacokinetic and pharmacodynamic parameters were compared. Of the 34 patients studied 16 (59%) died. Twenty patients had cultures positive for B. pseudomallei of whom 12 (60%) died. The median MIC90 of B. pseudomallei was 2 mg l(-1), giving a minimum target concentration (4*MIC) of 8 mg l(-1). The median (range) estimated total apparent volume of distribution, systemic clearance and terminal elimination half-lives of ceftazidime were 0.468 (0.241-0. 573) l kg(-1), 0.058 (0.005-0.159) l kg(-1) h(-1) and 7.74 (1.95-44.71) h, respectively. Clearance of ceftazidime and creatinine clearance were correlated closely (r = 0.71; P < 0.001) and there was no evidence of significant nonrenal clearance. Simulations based on these data and the ceftazidime sensitivity of the B. pseudomallei isolates indicated that administration by constant infusion would allow significant dose reduction and cost saving. With conventional 8 h intermittent dosing to patients with normal renal function, plasma ceftazidime concentrations could fall below the target concentration but this would be unlikely with a constant infusion. Correction for renal failure, which is common in patients with meliodosis is Clearance = k(*) creatinine clearance where k = 0.72. Calculation of a

  8. Effect of Heparin on Coagulation Tests: A Comparison of Continuous and Bolus Infusion in Haemodialysis Patients

    PubMed Central

    Nasiri, Ali Akbar; Ahmadidarrehsima, Sudabeh; Balouchi, Abbas; Moghadam, Mahdiye Poodine

    2016-01-01

    Introduction Haemodialysis is one of the most conventional treatments of chronic renal failure. The risk of clot formation is high during haemodialysis due to regular contact of blood with the surfaces of foreign objects such as catheters, dialyzers’ membrane, and other materials used for dialysis. Therefore, to prevent clot formation during haemodialysis, the dialysis system requires anticoagulation; this is usually done by heparin. Aim The present study aimed to compare two heparinization methods and determine the proper impacts of these methods. Materials and Methods In this quasi-experimental study, 80 haemodialysis patients covered by the dialysis center of Amir-al-momenin Hospital of Zabol were studied in two 40-member groups of heparin therapy methods of bolus injection and continuous infusion. PT and PTT were measured in blood samples collected from all patients before starting haemodialysis. The first group received 3000 units of heparin once the haemodialysis machine started to work and 2000 units of heparin two hours later as bolus injection. In the second group, 1500 units of heparin was injected at the start of dialysis after then, 5000 units of heparin (one mL) were mixed with 11 mL of distilled water and infused using a heparin injection pump up to half an hour before the end of dialysis. At 30 minutes after starting dialysis and at the end of 4 hours of haemodialysis, PT and PTT were measured and compared between the two groups. Results According to the results, the mean partial thromboplastin time in the bolus and continuous heparin-receiving group was 41.75±6.29 and 37.90±4.77, respectively, which was statistically significant (p=0.036). But PT was 14.45±1.82 in the bolus heparin group and 13.95±1.39 in the continuous heparin group, which was not significant according to the results of independent t-test (p=0.336). Conclusion The results indicated a statistically significant difference between the bolus heparin injection and the continuous

  9. The influence of continuous local wound infusion on postoperative pain in patients undergoing transfemoral amputation.

    PubMed

    Uhl, Christian; Betz, Thomas; Rupp, Andrea; Steinbauer, Markus; Töpel, Ingolf

    2015-09-01

    This pilot study was set up to examine the effects of a continuous postoperative wound infusion system with a local anaesthetic on perioperative pain and the consumption of analgesics. We included 42 patients in this prospective observational pilot study. Patients were divided into two groups. One group was treated in accordance with the WHO standard pain management protocol and in addition to that received a continuous local wound infusion treatment (Group 1). Group 2 was treated with analgesics in accordance with the WHO standard pain management protocol, exclusively. The study demonstrated a significantly reduced postoperative VAS score for stump pain in Group 1 for the first 5 days. Furthermore, the intake of opiates was significantly reduced in Group 1 (day 1, Group 1: 42.1 vs. Group 2: 73.5, p = 0.010; day 2, Group 1: 27.7 vs. Group 2: 52.5, p = 0.012; day 3, Group 1: 23.9 vs. Group 2: 53.5, p = 0.002; day 4, Group 1: 15.7 vs. Group 2: 48.3, p = 0.003; day 5, Group 1 13.3 vs. Group 2: 49.9, p = 0.001). There were no significant differences between the two groups, neither in phantom pain intensity at discharge nor postoperative complications and death. Continuous postoperative wound infusion with a local anaesthetic in combination with a standard pain management protocol can reduce both stump pain and opiate intake in patients who have undergone transfemoral amputation. Phantom pain was not significantly affected.

  10. Effects of continuous infusion of cholinergic drugs on memory impairment in rats with basal forebrain lesions.

    PubMed

    Miyamoto, M; Narumi, S; Nagaoka, A; Coyle, J T

    1989-02-01

    The effects of continuous infusion of cholinergic drugs on behavior in normal rats and on impaired acquisition and retention of several behavioral tasks in rats with basal forebrain (BF) lesions were investigated. Physostigmine and oxotremorine were infused continuously with a miniosmotic pump for 3 weeks, and the performance on several different behavioral tasks was examined during the infusion. In normal rats high doses of physostigmine (4 and 8 mg/kg/day s.c.) produced significant changes in general behavior and impaired performance in the Morris water maze. Oxotremorine (0.25-2 mg/kg/day s.c.) had no significant effects on general behavior or cognitive performance in normal rats, although severe cataracts developed at the high dose (4 mg/kg/day). A deficit in motor habituation in rats with BF lesions produced by bilateral injections of ibotenic acid (30 nmol on each side) was improved markedly by the chronic administration of physostigmine (2 mg/kg/day) and oxotremorine (1 mg/kg/day). BF lesions produced severe impairments in acquisition and retention in a passive avoidance task, an active avoidance and the Morris water maze, which was characterized by a marked disruption of retention. The impairment was also ameliorated markedly by the cholinergic drugs, whereas other behavioral impairments were not affected by the drugs. These results indicate that the continuous administration of cholinergic drugs produces a marked improvement of acquisition and retention in rats with BF lesions, and suggest that the impairment in cognitive performance, especially with regard to retention, caused by BF lesions is due to the disruption of the BF-cortical cholinergic pathway.

  11. Refractory Status Epilepticus in Children: Intention to Treat With Continuous Infusions of Midazolam and Pentobarbital.

    PubMed

    Tasker, Robert C; Goodkin, Howard P; Sánchez Fernández, Iván; Chapman, Kevin E; Abend, Nicholas S; Arya, Ravindra; Brenton, James N; Carpenter, Jessica L; Gaillard, William D; Glauser, Tracy A; Goldstein, Joshua; Helseth, Ashley R; Jackson, Michele C; Kapur, Kush; Mikati, Mohamad A; Peariso, Katrina; Wainwright, Mark S; Wilfong, Angus A; Williams, Korwyn; Loddenkemper, Tobias

    2016-10-01

    To describe pediatric patients with convulsive refractory status epilepticus in whom there is intention to use an IV anesthetic for seizure control. Two-year prospective observational study evaluating patients (age range, 1 mo to 21 yr) with refractory status epilepticus not responding to two antiepileptic drug classes and treated with continuous infusion of anesthetic agent. Nine pediatric hospitals in the United States. In a cohort of 111 patients with refractory status epilepticus (median age, 3.7 yr; 50% male), 54 (49%) underwent continuous infusion of anesthetic treatment. The median (interquartile range) ICU length of stay was 10 (3-20) days. Up to four "cycles" of serial anesthetic therapy were used, and seizure termination was achieved in 94% by the second cycle. Seizure duration in controlled patients was 5.9 (1.9-34) hours for the first cycle and longer when a second cycle was required (30 [4-120] hr; p = 0.048). Midazolam was the most frequent first-line anesthetic agent (78%); pentobarbital was the most frequently used second-line agent after midazolam failure (82%). An electroencephalographic endpoint was used in over half of the patients; higher midazolam dosing was used with a burst suppression endpoint. In midazolam nonresponders, transition to a second agent occurred after a median of 1 day. Most patients (94%) experienced seizure termination with these two therapies. Midazolam and pentobarbital remain the mainstay of continuous infusion therapy for refractory status epilepticus in the pediatric patient. The majority of patients experience seizure termination within a median of 30 hours. These data have implications for the design and feasibility of future intervention trials. That is, testing a new anesthetic anticonvulsant after failure of both midazolam and pentobarbital is unlikely to be feasible in a pediatric study, whereas a decision to test an alternative to pentobarbital, after midazolam failure, may be possible in a multicenter

  12. Responses of plasma glucose metabolism to exogenous insulin infusion in sheep-fed forage herb plantain and exposed to heat.

    PubMed

    Al-Mamun, M; Shibuya, K; Kajita, M; Tamura, Y; Sano, H

    2017-01-16

    The use of herbal plants as traditional medicines has a century long history. Plantain (Plantago lanceolata L.) is a perennial herb containing bioactive components with free radical scavenging activities. An isotope dilution technique using [U-13C]glucose was conducted to determine the effect of plantain on the responses of plasma glucose metabolism to exogenous insulin infusion in sheep. Six crossbred sheep (three wethers and three ewes; mean initial BW=40±2 kg) were fed either a mixed hay of orchardgrass (Dactylis glomerata) and reed canarygrass (Phalaris arundinacea) (MH-diet) or mixed hay and fresh plantain (1 : 1 ratio, dry matter basis, PL-diet) and exposed to a thermoneutral (TN, 20°C; 70% relative humidity (RH)) environment or a heat exposure (HE, 30°C; 70% RH) for 5 days using a crossover design for two 23-day periods. The isotope dilution was conducted on days 18 and 23 of the experimental period during TN and HE, respectively. Plasma concentration of α-tocopherol was greater (P<0.0001) for the PL-diet than the MH-diet and remained comparable between environmental treatments. Plasma glucose concentration before isotope dilution technique was reduced for sheep (P=0.05) during HE compared with TN and remained comparable between diets. Plasma glucose turnover rate during the preinfusion period of insulin did not differ (P=0.10) between dietary treatments and between environments (P=0.65). The response of plasma glucose utilization to exogenous insulin administration was lower (P=0.04) for the PL-diet than the MH-diet. Under present experimental conditions, the plantain group was found to be resistant to the effects of insulin infusion.

  13. Epidural analgesia during labor: continuous infusion or patient-controlled administration?

    PubMed

    Benhamou, D

    1995-05-01

    Patient-controlled epidural analgesia (PCEA) has several advantages over continuous epidural infusion of bupivacaine during labor: it produces a good analgesia with a limited sensory spread; generally, less bupivacaine is administered and maternal satisfaction with pain control is increased. However, the quality of analgesia is similar to that obtained with other forms of epidural administration. Moreover, PCEA is only a particular form of epidural and, as such, has the same safety requirements. PCEA does not appear to reduce the workload of the anesthetic team. The cost of the PCA pump will need to be included in future evaluation of the cost/benefit ratio.

  14. Neurotoxic Concentration of Piperacillin during Continuous Infusion in Critically Ill Patients.

    PubMed

    Quinton, Marie-Charlotte; Bodeau, Sandra; Kontar, Loay; Zerbib, Yoann; Maizel, Julien; Slama, Michel; Masmoudi, Kamel; Lemaire-Hurtel, Anne-Sophie; Bennis, Youssef

    2017-09-01

    This retrospective cohort study included 53 patients admitted to the intensive care unit (ICU), with an average age of 69 years, without neurologic disorder before initiation of a continuous piperacillin infusion at the standard dose and who underwent piperacillin serum concentration monitoring. Among them, 23 developed a neurologic disorder for which the piperacillin causality was chronologically and semiologically suggestive. A concentration threshold of 157.2 mg/liter independently predicted neurotoxicity with 96.7% specificity and 52.2% sensitivity and may constitute a limitation when targeting less susceptible pathogens. Copyright © 2017 American Society for Microbiology.

  15. A regular meal and insulin infusion regimen: its use in the treatment of acute-onset ketotic diabetes and in stabilization of poorly controlled established diabetic subjects.

    PubMed

    Davis, T M; Holman, R R; Eaton, P M; Turner, R C

    1982-01-01

    A simple regimen, consisting of a constant intravenous insulin infusion at either a basal, nocturnal rate or at a daytime rate matched by seven small, isocaloric meals taken every 2 h, has been applied to two clinical situations requiring optimal blood glucose control. In eight poorly controlled established diabetic subjects, quantitative estimates of daily insulin requirements were possible, with consequent improved control upon reinstitution of twice-daily subcutaneous insulin. In five acute-onset, ketotic diabetic subjects first treated by intravenous saline and low-dose intramuscular insulin, the regimen was used to achieve and maintain basal and postprandial normoglycemia. Ketonuria was abolished quickly in these patients, and falling insulin requirements and large doses of insulin were handled easily. In both clinical situations, subsequent subcutaneous insulin doses required little adjustment. The regimen is cheap, convenient to use, and widely applicable.

  16. Vancomycin intermittent dosing versus continuous infusion for treatment of ventilator-associated pneumonia in trauma patients.

    PubMed

    Schmelzer, Thomas M; Christmas, A Britton; Norton, H James; Heniford, B Todd; Sing, Ronald F

    2013-11-01

    Current guidelines for the empiric treatment of ventilator-associated pneumonia (VAP) recommend that vancomycin is dosed 15 mg/kg and administered twice daily for a target trough level of 15 to 20 μg/mL. This study compared conventional intermittent vancomycin infusion (IVI) with continuous vancomycin infusion (CVI). Our prospective, randomized study compared CVI with IVI in trauma patients with suspected VAP. The primary outcome measure was a serum vancomycin level within the target level 48 hours after initiation of therapy. Treatment groups were compared using standard statistical methods. The study included 73 patients, 36 IVI and 37 CVI. Eighteen patients were withdrawn from the study as a result of discontinuation of the drug before 48 hours or failure to draw levels at the appropriate time, resulting in 27 IVI and 28 CVI study patients. There were no differences between treatment groups in gender (P = 0.97), Injury Severity Score (P = 0.70), total body weight (P = 0.36), or age (P = 0.81). The mean serum vancomycin level for the IVI group was 8.9 ± 3.9 μg/mL, and the CVI level was 19.8 ± 6.13 μg/mL (P < 0.0001). Two patients in the IVI group (7.4%) were in the therapeutic range compared with 16 (57.1%) in the CVI group (P < 0.0001). Six patients in the CVI group (21.4%) and none of the IVI patients had supratherapeutic levels. Four patients developed renal insufficiency, three IVI (11.1%) and one CVI (3.6%) (P = 0.36). The current American Trauma Society dosing recommendations for vancomycin for presumptive VAP treatment are inadequate. Continuous vancomycin infusion should be adopted as the standard dosing strategy.

  17. The role of ranitidine infusion on glucose, insulin and C-peptide serum levels induced by oral glucose tolerance test in healthy subjects.

    PubMed

    Gentile, S; Marmo, R; Costume, A; Orlando, C; D'Alessandro, R; De Bellis, G; Porcellini, M; Coltorti, M

    1986-01-01

    In 9 healthy subjects we evaluated the effect of a constant ranitidine infusion (100 mg) on glucose (mg/dl), insulin (microU/ml) and C-peptide (ng/ml) serum levels promoted by oral glucose tolerance test (75 g). Ranitidine significantly increased the area under concentration/time curves for glucose and insulin but not that of C-peptide. Our data indicate that ranitidine does not affect pancreatic insulin release nor peripheral glucose utilization and are consistent with the hypothesis that ranitidine influences the hepatic clearance of glucose and insulin both of which undergo high first-pass liver extraction.

  18. The Influence of Insulin Injections and Infusions on Eating and Blood Glucose Level in the Rat,

    DTIC Science & Technology

    The effect of insulin on blood glucose and food intake in unanesthetized rats was studied under two conditions: (a) after a single intravenous...insulin into static obese hypothalamic subjects (whose daily food intake is fairly normal) leads to renewed hyperphagia, but the fluctuations in blood

  19. A phase I pharmacokinetic study of 21-day continuous infusion mitoxantrone.

    PubMed

    Greidanus, J; de Vries, E G; Mulder, N H; Sleijfer, D T; Uges, D R; Oosterhuis, B; Willemse, P H

    1989-06-01

    A phase I study of mitoxantrone given as a continuous infusion for 21 days using a venous access port and a portable pump was performed. The first dose step was 0.3 mg/m2/d for 21 days. Courses were repeated every 6 weeks. Dose increment per step was 0.1 mg/m2/d in the first three dose steps and 0.2 mg/m2/d in the latter dose steps. Twenty-five patients entered the study and received a total of 50 courses, with a median of two courses (range, one to five). Up to 0.5 mg/m2/d, no toxicity (according to the World Health Organization [WHO] criteria) occurred. At 0.7 mg/m2/d, one patient experienced grade 2 leukocytopenia and at the 0.9 mg/m2/d dose step, one patient experienced grade 2 leukocytopenia, grade 1 thrombocytopenia, and grade 1 hair loss. At 1.1 mg/m2/d, two of six patients had grade 3 leukocytopenia, and in one patient treatment was discontinued after two days because of myocardial infarction. In both patients receiving 1.3 mg/m2/d, treatment was discontinued after 2 weeks because of grade 3 leukocytopenia. Three patients at the 1.1 mg/m2/d, dose step and two patients at the 1.3 mg/m2/d dose step experienced some nausea in the last week of the infusion period. One patient developed subclavian vein thrombosis. No infectious complications occurred. Pharmacokinetic studies were performed by high-performance liquid chromatography (HPLC) with ultraviolet (UV) detection. Plasma steady-state was reached after 35 hours. During steady-state there was a linear relationship between the mitoxantrone dose administered and the level of mitoxantrone in plasma (r = .93, P less than .005). The mitoxantrone level in leukocytes increased significantly during the infusion period at the 0.9 mg/m2, the 1.1 mg/m2, and the 1.3 mg/m2 dose steps. The area under the curve (AUC) in leukocytes was higher with continuous infusion of 1.1 mg/m2/d for 21 days compared with bolus injection of 12 mg/m2. Mitoxantrone could be detected in plasma for at least five days after the end of the 21

  20. Safety and efficacy of continuous morphine infusions following pediatric cranial surgery in a surgical ward setting.

    PubMed

    Warren, Daniel T; Bowen-Roberts, Tim; Ou, Christine; Purdy, Robert; Steinbok, Paul

    2010-11-01

    Morphine is avoided by many neurosurgeons following cranial surgery. There exists a concern regarding the potential complications and a perception that cranial surgery is less painful than other surgical procedures. At British Columbia Children's Hospital continuous morphine infusions (CMI) have been used to control pain in pediatric neurosurgical patients. The purpose of this study was to compare the safety and efficacy of continuous intravenous morphine infusion to standard oral analgesics in a neurosurgical ward setting. A retrospective review of medical records for 71 children was completed. The patients underwent either cranial reconstruction (2002-2007) or craniotomies for intradural pathology (2005-2007) at British Columbia Children's Hospital. Outcome measures included pain control and adverse events. Comparison was made between patients receiving a CMI and patients receiving acetaminophen and codeine. Thirty-seven children received CMI on the ward (30 cranial reconstruction and 7 craniotomy), while 34 (10 cranial reconstruction and 24 craniotomy) received acetaminophen and codeine. There was no statistical difference in pain control. There was significantly more nausea on post-operative day one in the CMI group (p = 0.002). There were no other significant adverse events. These findings suggest that CMI is comparable to acetaminophen and codeine with respect to analgesia and serious side effects. We recommend the use of CMIs as an alternative when pain is poorly controlled in post-operative pediatric neurosurgical patients to prevent the potential adverse consequences of inadequate analgesia.

  1. Probable Nonconvulsive Status Epilepticus With the Use of High-Dose Continuous Infusion Ceftazidime.

    PubMed

    Collins, Reagan D; Tverdek, Frank P; Bruno, Jeffrey J; Coyle, Elizabeth A

    2016-12-01

    Multidrug resistant (MDR) bacterial infections are a major concern of health care providers due to their increasing incidence and associated mortality. In some cases, few or no antibiotics have preserved activity. Beta-lactam administration via continuous infusion can optimize time over minimum inhibitory concentration (MIC). In some cases, use of high-dose continuous infusion (HDCI) may be necessary to achieve serum levels in excess of nonsusceptible MIC values. The use of HDCI beta-lactams is not without risk, specifically neurotoxic adverse effects, which appear dose related. We describe a 64-year-old male who experienced myoclonus and nonconvulsive status epilepticus while receiving HDCI ceftazidime for treatment of multidrug resistant Pseudomonas aeruginosa bacteremia. This report serves as a cautionary example of the potential toxicities associated with HDCI beta-lactams and supports the importance of risk-benefit analysis prior to and during treatment. Additionally, the use of serum drug level monitoring may be necessary to better prevent or predict toxicity. © The Author(s) 2015.

  2. Pharmacokinetics of Continuous Infusion Meropenem With Concurrent Extracorporeal Life Support and Continuous Renal Replacement Therapy: A Case Report

    PubMed Central

    Moore, Wayne S.; Conley, Susan B.; Dickerman, Mindy J.; Small, Christine; Carella, Dominick; Shea, Paul; Parker, Jason; Chopra, Arun

    2016-01-01

    Pharmacokinetic parameters can be significantly altered for both extracorporeal life support (ECLS) and continuous renal replacement therapy (CRRT). This case report describes the pharmacokinetics of continuous-infusion meropenem in a patient on ECLS with concurrent CRRT. A 2.8-kg, 10-day-old, full-term neonate born via spontaneous vaginal delivery presented with hypothermia, lethargy, and a ~500-g weight loss from birth. She progressed to respiratory failure on hospital day 2 (HD 2) and developed sepsis, disseminated intravascular coagulation, and liver failure as a result of disseminated adenoviral infection. By HD 6, acute kidney injury was evident, with progressive fluid overload >1500 mL (+) for the admission. On HD 6 venoarterial ECLS was instituted for lung protection and fluid removal. On HD 7 she was initiated on CRRT. On HD 12, a blood culture returned positive and subsequently grew Pseudomonas aeruginosa with a minimum inhibitory concentration (MIC) for meropenem of 0.25 mg/L. She was started on vancomycin, meropenem, and amikacin. A meropenem bolus of 40 mg/kg was given, followed by a continuous infusion of 10 mg/kg/hr (240 mg/kg/day). On HD 15 (ECLS day 9) a meropenem serum concentration of 21 mcg/mL was obtained, corresponding to a clearance of 7.9 mL/kg/min. Repeat cultures from HDs 13 to 15 (ECLS days 7–9) were sterile. This meropenem regimen was successful in providing a target attainment of 100% for serum concentrations above the MIC for ≥40% of the dosing interval and was associated with a sterilization of blood in this complex patient on concurrent ECLS and CRRT circuits. PMID:26997934

  3. Continuous Lidocaine Infusions to Manage Opioid-Refractory Pain in a Series of Cancer Patients in a Pediatric Hospital.

    PubMed

    Gibbons, Kathleen; DeMonbrun, Andrea; Beckman, Elizabeth J; Keefer, Patricia; Wagner, Deb; Stewart, Margaret; Saul, D'Anna; Hakel, Stephanie; Liu, My; Niedner, Matthew

    2016-07-01

    Research on the safety and efficacy of continuous lidocaine infusions (CLIs) for the treatment of pain in the pediatric setting is limited. This article describes a series of pediatric oncology patients who received lidocaine infusions for refractory, longstanding, cancer-related pain. This is a retrospective review of patients who underwent lidocaine infusions to manage severe, opioid-refractory, cancer-related pain. Four patients ranging in age from 8 to 18 years were admitted to a pediatric hospital for their medical conditions and/or pain management. Structured chart review established demographic and diagnosis information, infusion rates, side effects, and efficacy of infusions in providing pain relief. Lidocaine bolus doses, infusion rates, serum concentrations, and subjective pain scores were analyzed. Median pain scores prior to lidocaine infusions were 8/10, falling to 2/10 at the infusion termination (P < 0.003), and rising to 3/10 in the first 24 hr after lidocaine (P < 0.029 compared to preinfusion pain). The infusions were generally well tolerated, with few side effects noted. In most cases, the improvement in pain scores persisted beyond termination of the infusion. CLIs were a helpful adjuvant in the four cases presented and may be an effective therapy for a more diverse array of refractory cancer pain. The majority of patients experienced pain relief well beyond the metabolic elimination of the lidocaine, corroborating a modulation effect on pain windup. Additional research regarding infusion rates, serum concentrations, side effects, and outpatient follow-up in a larger group of patients will provide additional insight into the role and safety of this therapy in children. © 2016 Wiley Periodicals, Inc.

  4. Alfaxalone for maintenance of anaesthesia in ponies undergoing field castration: continuous infusion compared with intravenous boluses.

    PubMed

    Deutsch, Julia; Ekiri, Abel; de Vries, Annemarie

    2017-04-14

    To compare alfaxalone as continuous intravenous (IV) infusion with intermittent IV injections for maintenance of anaesthesia in ponies undergoing castration. Prospective, randomized, 'blinded' clinical study. A group of 33 entire male Welsh ponies undergoing field castration. After preanaesthetic medication with IV detomidine (10 μg kg(-1)) and butorphanol (0.05 mg kg(-1)), anaesthesia was induced with IV diazepam (0.05 mg kg(-1)) followed by alfaxalone (1 mg kg(-1)). After random allocation, anaesthesia was maintained with either IV alfaxalone 2 mg kg(-1) hour(-1) (group A; n = 16) or saline administered at equal volume (group S; n = 17). When necessary, additional alfaxalone (0.2 mg kg(-1)) was administered IV. Ponies were breathing room air. Using simple descriptive scales, surgical conditions and anaesthesia recovery were scored. Total amount of alfaxalone, ponies requiring additional alfaxalone and time to administration, time from induction to end of infusion and end of infusion to standing were noted. Indirect arterial blood pressure, pulse and respiratory rates, end-expiratory carbon dioxide partial pressure and arterial haemoglobin oxygen saturation were recorded every 5 minutes. Data were analysed using Student t, Mann-Whitney U and chi-square tests, where appropriate (p < 0.05). Total amount of alfaxalone administered after induction of anaesthesia (0.75 ± 0.27 versus 0.17 ± 0.23 mg kg(-1); p < 0.0001) and time to standing (14.8 ± 4 versus 11.6 ± 4 minutes; p = 0.044) were higher in group A compared to group S. Ponies requiring additional alfaxalone boluses [four (group A) versus seven (group S)] and other measured variables were similar between groups; five ponies required oxygen supplementation [three (group A) versus two (group S)]. Continuous IV infusion and intermittent administration of alfaxalone provided similar anaesthesia quality and surgical conditions in ponies undergoing field castration. Less alfaxalone

  5. Qualitative and quantitative contrast enhanced ultrasonography of the pancreas using bolus injection and continuous infusion methods in normal dogs.

    PubMed

    Lim, Sue Yee; Nakamura, Kensuke; Morishita, Keitaro; Sasaki, Noboru; Murakami, Masahiro; Osuga, Tatsuyuki; Ohta, Hiroshi; Yamasaki, Masahiro; Takiguchi, Mitsuyoshi

    2013-12-30

    Quantitative contrast enhanced ultrasound is a major breakthrough for ultrasound imaging in recent years. However, contrast enhancement of the pancreas is brief with bolus injection. To assess if continuous infusion of Sonazoid(®) can prolong the duration of pancreatic enhancement over bolus injections, eight adult dogs received bolus injection and continuous infusion of Sonazoid(®) on separate days. Contrast enhanced ultrasound of the pancreatic parenchyma and proximal descending duodenum was performed, and time intensity curves reflecting tissue perfusions were generated. Perfusion parameters- time to initial upslope, peak time, time to wash-out and peak intensity were calculated and evaluated. Fast wash-in to intense peak, followed by rapid wash-out was observed for time intensity curves of bolus injection. With continuous infusion, contrast wash-in to peak intensity was gradual, followed by long plateau and slow wash-out. Median contrast enhancement durations of the pancreas and duodenum were significantly prolonged by continuous infusion from 11 sec (range, 10 to 23 sec) and 16 sec (range, 3 to 43 sec) at bolus injection to 205 sec (range, 170 to 264 sec, P<0.01) and 193 sec (range, 169 to 216 sec, P<0.05), respectively. Median peak intensity of the pancreas was 100.9 MPV (range, 80.2 to 124.3 MPV) at bolus injection and 77.6 MPV (range, 58.2 to 99.5 MPV, P<0.05) at continuous infusion. Prolonged continuous imaging is afforded by continuous infusion of contrast agent. Peak intensity of the pancreas was slightly diminished in continuous infusion, but offered adequate imaging subjectively.

  6. Response of rat model of Pneumocystis carinii pneumonia to continuous infusion of deferoxamine.

    PubMed Central

    Merali, S; Chin, K; Grady, R W; Weissberger, L; Clarkson, A B

    1995-01-01

    The iron-chelating drug deferoxamine mesylate (DFO) is active against Pneumocystis carinii in vitro and in rat and mouse models of P. carinii pneumonia. Because DFO has a short half-life, daily divided or continuous dosage was expected to improve the dose response, as is the case with DFO treatment of malaria. Therefore, results of single daily intraperitoneal injections were compared with results of an evenly divided four-times-daily dosage and the efficacy of delivery with implanted infusion pumps. The highest bolus dosage (1,000 mg kg-1 of body weight day-1) was as effective as the standard combination of trimethoprim with sulfamethoxazole. Unexpectedly, very little improvement was observed with the divided or continuous dosage, and several mechanisms that could account for this are discussed. PMID:7492082

  7. Changes in fat concentration of human milk during delivery by intermittent bolus and continuous mechanical pump infusion.

    PubMed

    Greer, F R; McCormick, A; Loker, J

    1984-11-01

    The changes in fat concentration and cumulative fat losses that occur during the delivery of human milk using two different continuous infusion systems were compared with the changes in fat concentration during simulated intermittent gavage or bolus feedings. With both mechanical pumps the largest cumulative fat losses and the greatest decreases in fat concentrations occurred at the slowest infusion rates. State of homogenization of the milk generally made little difference in the changes in fat concentration using the syringe pump, whereas homogenizing the milk increased the fat concentration significantly with the roller pump. With the syringe pump the positioning of the syringe tip (horizontal or vertical) made no difference in fat concentration at an infusion rate of 1 ml/hr, whereas at 4 and 7 ml/hr the fat concentration was increased significantly by keeping the syringe tip vertical. With either mechanical pump a large fat bolus was delivered during the eighth and final hour of infusion if the milk remaining in the tubing was recovered by using air infusion at the same infusion rate. Intermittent bolus delivery of human milk resulted in no significant loss of human milk fat, no changes in fat concentration, and no terminal delivery of a large fat load. Thus intermittent bolus feedings are preferred over continuous mechanical pump infusion systems for the delivery of human milk to low-birth-weight infants.

  8. Continuous intra-articular infusion of ropivacaine after unilateral total knee arthroplasty.

    PubMed

    Reeves, M; Skinner, M W

    2009-11-01

    Intra-articular infusion of local anaesthetic after joint arthroplasty is attractive in that it is simple and will not cause motor block. However the efficacy of the technique has yet to be established. We enrolled 66 patients scheduled for unilateral total knee arthroplasty under general anaesthesia and single-shot femoral and sciatic nerve blocks. All patients had an intra-articular Painbuster device sited at the end of the procedure. Patients were then randomised to control or one of two treatment arms - low-dose and high-dose ropivacaine. In the control group the balloon was filled with saline, in the low-dose group with 0.2% ropivacaine and in the high-dose group 0.375% ropivacaine. The catheters were infused continuously for 48 hours and then removed. Patients were followed up daily for three days to determine pain scores, opioid consumption and subjective assessment of the analgesic efficacy of the catheter Data were analysed for 30 controls and 31 in the treatment arms. Both groups were similar There were no significant differences between the control and treatment groups at all time points after adjustment for age. Patients in the high-dose group had higher pain scores and higher opioid consumption than the control groups from 24 to 48 hours. There were two cases of infection, both in the treatment groups. No positive benefit of intra-articular infusion of local anaesthetic after total knee arthroplasty could be identified. On the contrary there may be negative effects in terms of expense, pain and possibly infection risks.

  9. Pharmacokinetics of intravenous continuous rate infusions of sodium benzylpenicillin and ceftiofur sodium in adult horses.

    PubMed

    Edwards, Scott H; Khalfan, Shahid A; Jacobson, Glenn A; Pirie, Adam D; Raidal, Sharanne L

    2017-01-01

    OBJECTIVE To determine plasma drug concentrations after IV administration of a bolus followed by continuous rate infusion (CRI) of sodium benzylpenicillin and ceftiofur sodium to healthy adult horses. ANIMALS 6 Thoroughbred mares (3 to 9 years old; mean ± SD body weight, 544 ± 55 kg) with no history of recent antimicrobial treatment. PROCEDURES Horses were used in 2 experiments conducted 14 days apart. For each experiment, horses were housed individually in stables, and catheters were placed bilaterally in both jugular veins for drug administration by CRI (left catheter) and for intermittent collection of blood samples (right catheter). Synovial fluid samples were obtained from carpal joints following ceftiofur administration to evaluate drug diffusion into articular spaces. RESULTS Plasma concentrations above accepted minimum inhibitory concentrations for common pathogens of horses were achieved within 1 minute after bolus administration and remained above the minimum inhibitory concentration for 48 (ceftiofur) or 12 (benzylpenicillin) hours (ie, the duration of the CRI). Mean synovial fluid ceftiofur free acid equivalent concentrations were approximately 46% (range, 25.4% to 59.8%) of plasma concentrations at the end of infusion. CONCLUSIONS AND CLINICAL RELEVANCE Compared with intermittent bolus administration, the loading dose and CRI used less drug but maintained high plasma concentrations for the duration of infusion. By use of pharmacological parameters derived in this study, a loading dose of 2.5 mg/kg and CRI of 200 μg/kg/h should achieve plasma ceftiofur concentrations of 4 μg/mL; a loading dose and CRI of 1.3 mg/kg and 2.5 μg/kg/h, respectively, should achieve plasma benzylpenicillin concentrations of 2 μg/mL.

  10. The Development of Recurrent Seizures after Continuous Intrahippocampal Infusion of Methionine Sulfoximine in Rats

    PubMed Central

    Wang, Yue; Zaveri, Hitten P.; Lee, Tih-Shih W; Eid, Tore

    2009-01-01

    Glutamine synthetase is deficient in astrocytes in the epileptogenic hippocampus in human mesial temporal lobe epilepsy (MTLE). To explore the role of this deficiency in the pathophysiology of MTLE, rats were continuously infused with the glutamine synthetase inhibitor methionine sulfoximine (MSO, 0.625 µg/h) or 0.9% NaCl (saline control) unilaterally into the hippocampus. The seizures caused by MSO were assessed by video-intracranial electroencephalogram (EEG) monitoring. All (28 of 28) of the MSO-treated animals and none (0 of 12) of the saline-treated animals developed recurrent seizures. Most recurrent seizures appeared in clusters of 2 days’ duration (median; range, 1 to 12 days). The first cluster was characterized by frequent, predominantly Stage I seizures, which presented after the first 9.5 h of infusion (median; range, 5.5 to 31.7 h). Subsequent clusters of less-frequent, mainly partial seizures occurred after a clinically silent interval of 7.1 days (median; range, 1.8 to 16.2 days). The ictal intracranial EEGs shared several characteristics with recordings of partial seizures in humans, such as a distinct evolution of the amplitude and frequency of the EEG signal. The neuropathology caused by MSO had similarities to hippocampal sclerosis in 23.1% of cases, whereas 26.9% of the animals had minimal neuronal loss in the hippocampus. Moderate to severe diffuse neuronal loss was observed in 50% of the animals. In conclusion, the model of intrahippocampal MSO infusion replicates key features of human MTLE and may represent a useful tool for further studies of the cellular, molecular and electrophysiological mechanisms of this disorder. PMID:19747915

  11. Continuous Infusion of Ketamine for Out-of-hospital Isolated Orthopedic Injuries Secondary to Trauma: A Randomized Controlled Trial.

    PubMed

    Wiel, Eric; Zitouni, Djamel; Assez, Nathalie; Sebilleau, Quentin; Lys, Sébastien; Duval, Audrey; Mauriaucourt, Patrick; Hubert, Hervé

    2015-01-01

    Abstract Objective. Although ketamine has recently been demonstrated to provide a morphine-sparing effect, no previous study reports the effect of continuous infusion of ketamine for analgesia in out-of-hospital environments. The aim of this study was to compare the effect of a continuous infusion of ketamine (IK group) vs. a continuous infusion of saline (IS group) on morphine requirements in out-of-hospital trauma patients suffering from severe acute pain. Methods. In this prospective, multicenter, randomized, single-blind clinical study, patients suffering from isolated orthopedic injuries secondary to trauma with severe acute pain received a low-dose intravenous (IV) bolus of ketamine (0.2 mg·kg(-1)) combined with an IV bolus of morphine (0.1 mg·kg(-1)) and were randomized either in the IK group (IV continuous infusion of ketamine 0.2 mg·kg(-1)·h(-1)), or in the IS group (IV continuous infusion of saline at the same volume). The primary endpoint was morphine requirements in terms of total dose of morphine (excluding the baseline bolus) injected at the end of prehospital emergency care at hospital admission (final time, Tf). The secondary endpoint was evaluation of pain with visual analogic scale (VAS). Results. Sixty-six patients were enrolled. Total morphine dose was not significantly reduced with continuous infusion of ketamine (0.048 [0.000; 0.150] vs. 0.107 [0.052; 0.150] in IK and IS groups), with similar mean duration of care (median 35.0 min). Analgesia was as efficient without any significant difference in VAS at Tf between groups (3.1 ± 2.3 (IK group) vs. 3.7 ± 2.7 (IS group), p = 0.5). Conclusions. Continuous ketamine infusion did not reduce morphine requirements in severe acute pain trauma patients in the out-of-hospital emergency settings.

  12. Continuous Regional Arterial Infusion Therapy for Acute Necrotizing Pancreatitis Due to Mycoplasma pneumoniae Infection in a Child

    SciTech Connect

    Nakagawa, Motoo Ogino, Hiroyuki; Shimohira, Masashi; Hara, Masaki; Shibamoto, Yuta

    2009-05-15

    A case of acute necrotizing pancreatitis due to Mycoplasma pneumoniae infection was treated in an 8-year-old girl. She experienced acute pancreatitis during treatment for M. pneumoniae. Contrast-enhanced computed tomographic scan revealed necrotizing pancreatitis. The computed tomographic severity index was 8 points (grade E). A protease inhibitor, ulinastatin, was provided via intravenous infusion but was ineffective. Continuous regional arterial infusion therapy was provided with gabexate mesilate (FOY-007, a protease inhibitor) and meropenem trihydrate, and the pancreatitis improved. This case suggests that infusion therapy is safe and useful in treating necrotizing pancreatitis in children.

  13. Effects of abomasal infusion of tallow or camelina oil on responses to glucose and insulin in dairy cows during late pregnancy.

    PubMed

    Salin, S; Taponen, J; Elo, K; Simpura, I; Vanhatalo, A; Boston, R; Kokkonen, T

    2012-07-01

    Late pregnancy is associated with moderate insulin resistance in ruminants. Reduced suppression of lipolysis by insulin facilitates mobilization of nonesterified fatty acids (NEFA) from adipose tissue, resulting in elevated plasma NEFA concentrations. Decrease in dry matter intake (DMI) before parturition leads to accelerated lipomobilization and increases plasma NEFA, which may further impair insulin sensitivity. The aim of the study was to evaluate the effects of elevation of plasma NEFA concentration by abomasal infusions tallow (TAL) or camelina oil (CAM) on whole-body responses to exogenous glucose and insulin. We further assessed whether CAM, rich in C18:3n-3, enhances whole-body insulin sensitivity compared with TAL. Six late-pregnant, second-parity, rumen-cannulated dry Ayrshire dairy cows fed grass silage to meet 95% of metabolizable energy requirements were used in a replicated 3 × 3 Latin square with 5-d periods and 5 recovery days between each period. Treatments consisted of abomasal infusion of 500 mL/d (430 g of lipids/d) of water (control), TAL, or CAM administered in 10 equal doses daily. Intravenous glucose tolerance test (IVGTT) and i.v. insulin challenge (IC) were performed on d 5 after 98 and 108 h of treatment infusions, respectively. Infusion of lipids increased basal plasma NEFA concentrations on d 5 (CAM: 0.25; TAL: 0.28; control: 0.17 mmol/L). Following glucose injection, the rate of glucose clearance (CR) was lower in lipid-treated cows (CAM: 1.34; TAL: 1.48; control: 1.74%/min) and time to reach half-maximal glucose concentration (T(1/2)) was longer (CAM: 54; TAL: 47; control: 42 min). Similar responses were observed after insulin injection. Increased plasma NEFA concentration tended to decrease insulin secretion in IVGTT. Infusion of CAM increased plasma C18:3n-3 content (CAM: 26.4; TAL: 16.1; control: 20.9 g/100g of fatty acids). Data suggest that CAM had an insulin-sensitizing effect, because the disposition index and insulin

  14. Postoperative continuous paravertebral anesthetic infusion for pain control in lumbar spinal fusion surgery.

    PubMed

    Elder, James B; Hoh, Daniel J; Wang, Michael Y

    2008-01-15

    A retrospective, case-control study was conducted to analyze postoperative outcomes in patients who received local anesthetic infusion pumps after lumbar spinal fusion procedures. Data were collected prospectively via nursing protocol and third party assessment, and analyzed retrospectively. To review the safety and efficacy of continuous infusion of local anesthetic into the subfascial aspects of the wound after lumbar fusion surgery for treatment of postoperative pain, and to determine whether other outcome measures such as postoperative nausea and vomiting, ambulation and length of hospitalization were affected by the presence of the device. Patients who undergo lumbar spine fusion procedures frequently experience significant, debilitating pain related to their surgery. This pain may delay postoperative mobilization, increase length of hospitalization, and require prolonged use of high doses of narcotics. Use of a local anesthetic continuous-infusion pump after surgery may lead to improvements in these outcome variables. After posterior lumbar spine fusion procedures, 26 consecutive patients received the ON-Q PainBuster, which infused 0.5% marcaine via an elastomeric pump into the subfascial aspects of the wound. Retrospective analysis compared each of these patients with a case-matched control patient. Data included pain scores and opiate use during the first 5 postoperative days (PODs), length of hospital stay, and complications. Variables such as age, American Society of Anesthesiologists (ASA) physical status, and surgical procedure were similar between matched cases. One patient was excluded because of active heroine abuse. Patients with the ON-Q PainBuster used 41.2% less narcotics on POD 1, 50.1% less on day 2, and 47.1% less on day 3 compared with the control patients. Differences in opiate usage were not statistically significant on POD 4 (45.5% less) and 5 (50.3% less). A lower average pain score was observed among patients with the ON-Q PainBuster on

  15. A continuous [{sup 15}O]H{sub 2}O production and infusion system for PET imaging

    SciTech Connect

    Sajjad, Munawwar; Liow, Jeih-San

    1999-06-10

    A system for continuous production and infusion of [{sup 15}O]H{sub 2}O has been designed for PET cerebral blood flow studies. The injection system consists of a four-port-two-position valve, two Horizon Nxt infusion pumps, and a sterile 50 ml vial. The variation of the production of [{sup 15}O]H{sub 2}O was <1%. The variation of activity delivered measured by scanner counts during the steady state period was <2%.

  16. Continuous Infusion of 20-Hydroxyecdysone Increased Mass of Triceps Brachii in C57BL/6 Mice

    PubMed Central

    Cheng, Diana M.; Kutzler, Louis W.; Boler, Dustin D.; Drnevich, Jenny; Killefer, John; Lila, Mary Ann

    2012-01-01

    Phytoecdysteroids have been attributed with numerous pharmacological properties in animals, including increasing muscle mass, and 20-hydroxyecdysone (20E) is one of the most abundant phytoecdysteroids produced by plants. In this study, the physiological and gene expression effects of 20E were analyzed in C57BL/6 mice given a continuous infusion of saline or 20E (5 mg/kg/day) for 5 or 15 d using subcutaneously implanted Alzet® osmotic pumps. The masses of the total body, muscle groups and organs were determined. There was a significant increase (p = 0.01) in the mass of triceps brachii in mice treated with 20E for 5 d (115 +/− 8 mg) compared to mice treated with saline for 5 d (88 +/− 3 mg), however, there were no differences in the other measured parameters. To determine potential mechanisms of 20E in skeletal muscle, Illumina’s Mouse Whole Genome-6 v2.0 Expression BeadChips were used to evaluate changes in gene expression of the triceps brachii after 20E infusion. Ingenuity Pathways Analysis was used to identify genes with the most evidence for differential expression, of which, 16 genes involved in the skeletal and muscular system were identified. Overall, the data suggests that 20E does not have potent anabolic properties, however, a muscle-specific increase was observed and genes were identified to provide an explanation for the muscle accretion. PMID:22495969

  17. Continuous infusion, general anesthesia and other intensive care treatment for uncontrolled status epilepticus.

    PubMed

    Tasker, Robert C; Vitali, Sally H

    2014-12-01

    To discuss the use of continuous infusions, general anesthesia, hypothermia, and ketogenic diet as treatment for uncontrolled status epilepticus in pediatric patients. Recent studies demonstrate that clinical practitioners have a hierarchy in approach in controlling refractory status epilepticus (RSE) and super-refractory status epilepticus in children. In the acute setting of RSE, midazolam achieves clinical seizure control at a mean of 41 min after starting an infusion. When midazolam has failed to control RSE, the evidence points to barbiturate anesthesia as the next frequently used option. When both midazolam and barbiturates have failed, use of isoflurane or ketamine anesthesia has been tried at a mean of 10 days after RSE onset, although the studies are largely anecdotal. Increasingly, the use of therapeutic hypothermia or ketogenic diet is described as a strategy for super-refractory status epilepticus, and better evidence for their use may become available from ongoing randomized studies. Uncontrolled episodes of status epilepticus require intensive care treatment and the literature describes a common pathway of care used by many. However, cases of truly refractory and super-refractory status epilepticus are seen infrequently at any given institution. One strategy to improve the quality of evidence is to develop prospective, national and multinational case registries to determine the range of presentations and causes, efficacy of treatments, and clinical outcomes.

  18. Infection risk and stability of a continuous 8-h 250 mL rFVIII infusion.

    PubMed

    Lambing, A; Kuriakose, P; Mueller, L M

    2014-03-01

    This study seeks to identify the delivery method of continuous infusion using a 250 cc IV bag via pump, change every 8 h. Additionally, the study will examine the infection risk with the use of 8 h infusions. Ten hemophilia A patients were identified for the study. Each patient received a bolus factorVIII (FVIII) infusion with a pre FVIII level and 1 h post FVIII level to determine recovery levels for optimal dosing. On the day of 8-h continuous infusion, the pt received a bolus VIII (Kogenate FS (™)) for correction to 100% followed by individually calculated continuous infusion (Kogenate FS (™)) FVIII. FVIII levels were drawn from the IV bag and peripherally from the patient in the opposite arm at time points: pre infusion, 1, 2, 3, 4, 5, 6 and 8 h. Additionally, blood cultures were drawn from the IV bag and from the IV tubing at time points pre infusion, 4 and 8 h. Fourteen subjects agreed to participate in the study; 4 failed to follow up, hence 10 subjects were included in the analysis of data; 7 severe, 2 moderate, and 1 mild hemophilia A. Age range was 26-62 years. Ethnic breakdown included 5 African American, 4 Caucasian, 1 Hispanic. With all infusions, the range of FVIII was 65-135% (blood) and 62-200% (bag). After the start of infusion, there were no significant differences noted between the hourly FVIII levels in the subjects and the IV values (P-value range 0.36-0.9). Additionally, given three time points with six cultures per patient, totaling 60 points of cultures drawn for the study, all cultures from the IV bag and patient were negative. The effective delivery method and safety of an 8-h continuous infusion of FVIII (Kogenate FS (™)) has been confirmed. This method can be helpful given that many hospitals may not carry the required mini-pumps, allowing a standard safe delivery of FVIII (Kogenate FS (™)) continuous infusion by available means.

  19. Postoperative continuous paravertebral anesthetic infusion for pain control in posterior cervical spine surgery: a case-control study.

    PubMed

    Elder, James B; Hoh, Daniel J; Liu, Charles Y; Wang, Michael Y

    2010-03-01

    Patients who undergo posterior cervical spinal fusion procedures frequently experience significant postoperative pain. Use of a local anesthetic continuous infusion pump after surgery may improve these outcome variables. After posterior cervical spine fusion procedures, 25 consecutive patients received continuous infusion of 0.5% bupivacaine into the subfascial aspects of the wound via an elastomeric pump. Data were collected prospectively by third party assessment using standard nursing protocols. This included numeric pain scores and opiate use over the first 4 postoperative days (PODs), length of hospitalization, and complications. In a retrospective analysis, we compared each study patient to a control patient who did not receive the continuous infusion of bupivacaine. Demographic variables and surgical procedure were similar among matched cases. Patients receiving continuous local anesthetic infusion used significantly less narcotics (P < .05) during the first 4 PODs: 24.4% on day 1, 34.1% on day 2, 53.5% on day 3, and 58.1% on day 4. A lower average pain score was observed among study patients on each POD (P < .05): 31.5% less on day 1, 13.0% on day 2, 24.0% on day 3, and 35.7% on day 4. Patients with the infusion device were discharged home earlier (POD 4.9 versus 6.7; P = .024) and demonstrated improvement in time to ambulation, first bowel movement, and discontinuation of the patient-controlled analgesia machine. No complications were associated with the device. Patients with the local anesthetic continuous infusion device required less narcotics and reported lower pain scores than control patients on each of the first 4 PODs. These results suggest that continuous infusion of local anesthetic into the paravertebral tissue during the immediate postoperative period is a safe and effective technique that achieves lower pain scores and narcotic use and improves multiple postoperative outcome variables.

  20. Plasma and peritoneal concentration following continuous infusion of cefotaxime in patients with secondary peritonitis.

    PubMed

    Seguin, Philippe; Verdier, Marie Clémence; Chanavaz, Charles; Engrand, Charlotte; Laviolle, Bruno; Donnio, Pierre-Yves; Mallédant, Yannick

    2009-03-01

    The aim of this study was to determine the steady-state plasma and peritoneal concentrations of cefotaxime and its metabolite desacetyl-cefotaxime administered by continuous infusion to critically ill patients with secondary peritonitis. In 11 patients, a continuous infusion of 4 g/24 h of cefotaxime following a bolus of 2 g was evaluated. Plasma and peritoneal levels of cefotaxime and desacetyl-cefotaxime were measured at steady state on days 2 and 3 (plasma) and on day 3 (peritoneal) by HPLC. Results are expressed as means +/- SD. Total and unbound plasma levels of cefotaxime were 24.0 +/- 21.5 and 20.3 +/- 19.8 mg/L on day 2 and 22.1 +/- 20.7 and 18.9 +/- 19.2 mg/L on day 3, respectively. Total and unbound levels of cefotaxime in the peritoneal fluids were 16.2 +/- 11.5 and 14.3 +/- 10.4 mg/L, respectively. The unbound fraction of plasma cefotaxime was 81.8 +/- 5.9% on day 2 and 82.6 +/- 7.7% on day 3, and the unbound fraction at the peritoneal site was 87.0 +/- 5.5% on day 3. Total and unbound plasma levels of desacetyl-cefotaxime were 9.0 +/- 8.1 and 8.4 +/- 8.1 mg/L on day 2 and 7.6 +/- 7.6 and 7.2 +/- 7.6 mg/L on day 3, respectively. Total and unbound levels of desacetyl-cefotaxime in the peritoneal fluids were 11.9 +/- 11.5 and 10.9 +/- 10.8 mg/L, respectively. The MICs for the enterobacteria recovered ranged from 0.016 to 0.25 mg/L. Continuous infusion of 4 g/24 h of cefotaxime provided a peritoneal concentration >5x MIC for the recovered Enterobacteriaceae and the susceptibility breakpoint of cefotaxime for facultative Gram-negative bacilli.

  1. Optimising antiemesis in cancer chemotherapy: efficacy of continuous versus intermittent infusion of high dose metoclopramide in emesis induced by cisplatin.

    PubMed Central

    Warrington, P S; Allan, S G; Cornbleet, M A; MacPherson, J S; Smyth, J F; Leonard, R C

    1986-01-01

    Thirty three untreated patients being given cisplatin received metoclopramide (7 mg/kg) for antiemesis by either continuous or intermittent infusion in a random order. Each patient received intravenous dexamethasone in addition. High pressure liquid chromatography was used to measure plasma concentrations of metoclopramide. The two regimens were evaluated for antiemetic efficacy and the incidence of side effects. The intermittent metoclopramide regimen resulted in peak and trough plasma concentrations of metoclopramide with accumulation at eight hours, while the loading dose and continuous infusion resulted in mean plasma concentrations greater than 0.85 micrograms/ml (2.8 mumol/l) throughout the eight hour period. The continuous infusion was associated with a significant improvement in nausea and vomiting and reduction in diarrhoea. Major control of emesis (two episodes or fewer) was achieved in 27 patients receiving continuous metoclopramide compared with 18 receiving intermittent metoclopramide. PMID:3790968

  2. Stability and Compatibility of Ceftazidime Administered by Continuous Infusion to Intensive Care Patients

    PubMed Central

    Servais, Hélène; Tulkens, Paul M.

    2001-01-01

    The stability and compatibility of ceftazidime have been examined in the context of its potential use in concentrated solutions for continuous infusion in patients suffering from severe nosocomial pneumonia and receiving other intravenous medications by the same route. Ceftazidime stability in 4 to 12% solutions was found satisfactory (<10% degradation) for 24 h if kept at a temperature of 25°C (77°F) maximum. Studies mimicking the simultaneous administration of ceftazidime and other drugs as done in clinics showed physical incompatibilities with vancomycin, nicardipine, midazolam, and propofol and a chemical incompatibility with N-acetylcystein. Concentrated solutions (50 mg/ml) of erythromycin or clarithromycin caused the appearance of a precipitate, whereas gentamicin, tobramycin, amikacin, isepamicin, fluconazole, ketamine, sufentanil, valproic acid, furosemide, uradipil, and a standard amino acid solution were physically and chemically compatible. PMID:11502544

  3. A wearable optical device for continuous monitoring during neoadjuvant chemotherapy infusions

    NASA Astrophysics Data System (ADS)

    Teng, Fei; Cormier, Timothy; Sauer-Budge, Alexis; Roblyer, Darren M.

    2016-03-01

    We present a new continuous-wave (CW) wearable diffuse optical device aimed at investigating the hemodynamic response of locally advanced breast cancer patients during a patient's first neoadjuvant chemotherapy infusion. The system consists of a flexible substrate that supports an array of surface-mount LED and photodiode pairs (i.e. optodes). Probe performance was evaluated using solid tissue-simulating phantoms. Measurements revealed high SNR (65dB), low source-detector crosstalk (-59 dB), high measurement precision (0.17%), and good thermal stability (0.2% Vrms/°C). A cuff occlusion experiment was performed on the forearm of a healthy volunteer to demonstrate the ability to track rapid hemodynamic changes.

  4. Antibiotic prophylaxis in bariatric surgery with continuous infusion of cefazolin: determination of concentration in adipose tissue.

    PubMed

    Anlicoara, Rafael; Ferraz, Álvaro A B; da P Coelho, Kilma; de Lima Filho, José L; Siqueira, Luciana T; de Araújo, José G C; Campos, Josemberg M; Ferraz, Edmundo M

    2014-09-01

    The aim of this study was to evaluate the concentration of cefazolin in adipose tissue of patients undergoing bariatric surgery. Eighteen patients undergoing bariatric surgery were evaluated during the period from October 2011 to May 2012. All patients had a dosage schedule of antibiotic prophylaxis with cefazolin administered as follows: first, 2 g in anesthetic induction, followed by continuous infusion of 1 g diluted in 250 ml of saline solution. Adipose samples, collected soon after the incision (initial) and before the skin synthesis (final), were analyzed using reverse phase high-pressure liquid chromatography. The level of significance adopted was 5 %. The cefazolin concentration in the adipose tissue samples at the beginning of surgery was an average of 6.66 ± 2.56 ug/ml. The mean concentration before the skin synthesis was 7.93 ± 2.54 ug/ml. Patients with BMI < 40 kg/m(2) had higher initial and final sample concentrations of cefazolin than patients with BMI ≥ 40 kg/m(2). There was no surgical site infection (SSI) in any of the patients. In bariatric surgeries, addition of a 1 g increase of cefazolin, administered through continuous intravenous infusion, to the currently recommended dose of 2 g administered in anesthetic induction provided a concentration in the adipose tissue above the minimum inhibitory concentration (MIC) of the main causal agents of SSI. An inverse correlation between BMI and concentration of cefazolin in adipose tissue was observed.

  5. INFLUENCE OF MECHANICAL VENTILATION ON VANCOMYCIN PHARMACOKINETICS ADMINISTERED BY CONTINUOUS INFUSION IN CRITICALLY ILL PATIENTS.

    PubMed

    Medellín-Garibay, Susanna Edith; Romano-Moreno, Silvia; Tejedor-Prado, Pilar; Rubio-Álvaro, Noelia; Rueda-Naharro, Aida; Blasco-Navalpotro, Miguel Angel; García, Benito; Barcia, Emilia

    2017-09-11

    Pathophysiological changes involved on drug disposition in critically ill patients, should be considered on the dosing optimization of vancomycin administered by continuous infusion, and certain strategies must be applied to reach therapeutic targets on the first day of treatment. The aim of this study was to develop a population pharmacokinetic model of vancomycin to determine clinical covariates, including mechanical ventilation, that influence the wide variability of this antimicrobial. Vancomycin plasma concentrations from 54 critically ill patients were simultaneously analyzed by population pharmacokinetic approach. A nomogram was developed for dosing recommendations and was internally evaluated throughout stochastic simulations. The vancomycin plasma concentration versus time data were best described by a one-compartment open model with exponential inter-individual variability associated to vancomycin clearance and volume of distribution. Residual error followed a homoscedastic trend. Creatinine clearance and body weight significantly dropped the objective function value, showing their influence on vancomycin clearance and volume of distribution, respectively. Characterization based on the presence of mechanical ventilation, demonstrated a decreasing value of 20% on vancomycin clearance. External validation (n=18) was performed to evaluate the prediction ability of the model with median bias and precision values of 0.7 mg/L (95%CI -0.4, 1.7) and 5.9 mg/L (95%CI 5.4, 6.4), respectively. A population pharmacokinetic model was developed for the administration of vancomycin by continuous infusion in critically ill patients, demonstrating the influence of creatinine clearance and mechanical ventilation on vancomycin clearance, as well as the implications on dosing rates to reach therapeutic range (20-30 mg/L). Copyright © 2017 American Society for Microbiology.

  6. [Successful management of neurosurgical procedures with continuous infusion of recombinant factor IX in a child with hemophilia B].

    PubMed

    Yamamoto, Mariko; Nakadate, Hisaya; Iguchi, Umefumi; Masuda, Hiroshi; Sakai, Hirokazu; Ishiguro, Akira

    2013-03-01

    This report describes the successful management of neurosurgical procedures with continuous infusion of recombinant factor IX (rFIX). A 1-year-old boy with severe hemophilia B was administered prophylactic therapy with rFIX after intracranial bleeding. We found the enlargement of an arachnoid cyst in a follow-up CT scan. He underwent marsupialization of the cyst under the continuous infusion of rFIX. FIX levels were examined in our hospital and the rFIX infusion rate was adjusted in an attempt to keep FIX levels above 90% intraoperatively, and 70% until his 7th post-operative day. We studied the pharmacokinetic profile of rFIX and found a half-time of 25 hours and mean in vivo recovery of 0.69 IU/dl/IU/kg. Reconstituted rFIX also retained at least 95% activity after 72 hours at room temperature. This is the first report of the perioperative management of a child undergoing a neurosurgical procedure under the continuous infusion of rFIX in Japan. Further studies are required before the routine use of this product for continuous infusion.

  7. Electroencephalographic Recovery, Hypnotic Emergence, and the Effects of Metabolite Following Continuous Infusions of a Rapidly Metabolized Etomidate Analog in Rats

    PubMed Central

    Pejo, Ervin; Ge, Rile; Banacos, Natalie; Cotten, Joseph F.; Husain, S. Shaukat; Raines, Douglas E.

    2012-01-01

    Background Methoxycarbonyl etomidate is an ultra-rapidly metabolized etomidate analog. It is metabolized to methoxycarbonyl etomidate carboxylic acid (MOC-ECA), which has a hypnotic potency that is 350-fold lower than that of methoxycarbonyl etomidate. We explored the relationships between methoxycarbonyl etomidate infusion duration, recovery time, metabolite concentrations in blood and cerebrospinal fluid (CSF), and methoxycarbonyl etomidate metabolism in brain tissue and CSF to test the hypothesis that rapid metabolism of methoxycarbonyl etomidate may lead to sufficient accumulation of MOC-ECA in the brain to produce a pharmacological effect. Methods A closed-loop system with burst suppression ratio feedback was used to administer methoxycarbonyl etomidate infusions of varying durations to rats. After infusion, recovery of the electroencephalogram and righting reflexes were assessed. MOC-ECA concentrations were measured in blood and CSF during and after methoxycarbonyl etomidate infusion and the in vitro half-life of methoxycarbonyl etomidate was determined in rat brain tissue and CSF. Results Upon terminating continuous methoxycarbonyl etomidate infusions, the burst suppression ratio recovered in a biexponential manner with fast and slow components having time constants that differed by more than 100-fold and amplitudes that varied inversely with infusion duration. MOC-ECA concentrations reached hypnotic levels in the CSF with prolonged methoxycarbonyl etomidate infusion and then fell over several hours after infusion termination. The metabolic half-life of methoxycarbonyl etomidate in brain tissue and CSF was 11 and 20 min, respectively. Conclusion In rats, methoxycarbonyl etomidate metabolism is sufficiently fast to produce pharmacologically active MOC-ECA concentrations in the brain with prolonged methoxycarbonyl etomidate infusion. PMID:22417966

  8. Antimicrobial effect of continuous lidocaine infusion in a Staphylococcus aureus-induced wound infection in a mouse model.

    PubMed

    Lu, Cheng-Wei; Lin, Tzu-Yu; Shieh, Jiann-Shing; Wang, Ming-Jiuh; Chiu, Kuan-Ming

    2014-11-01

    Continuous infusion of local anesthetics in surgical wounds has been shown to be an effective technique for postoperative analgesia. To investigate the potential antimicrobial effect of continuous local anesthetic infusion, we adapted a mouse model of surgical wound infection to examine effects on antibacterial response. Forty male BALB/c mice were randomized into 2 groups. An incision wound was made over the dorsal flank and instilled with Staphylococcus aureus. An osmotic pump was then implanted to deliver either 0.9% NaCl or 2% lidocaine continuously. Each wound was cultured postoperatively at 2 days, and the colony count of S. aureus was determined. Results showed that the number of colony-forming units of S. aureus measured in wounds treated with lidocaine displayed a nearly 10-fold reduction compared to the wounds in the saline group (P=0.009). The demonstrated antibacterial activity indicates that local anesthetic infusion may play a role in prophylaxis for surgical wound infections.

  9. The hyperinsulinaemic-euglycaemic glucose clamp: reproducibility and metabolic effects of prolonged insulin infusion in healthy subjects.

    PubMed

    Soop, M; Nygren, J; Brismar, K; Thorell, A; Ljungqvist, O

    2000-04-01

    To examine the reproducibility of the hyperinsulinaemic-euglycaemic clamp technique at mid-physiological hyperinsulinaemia, seven healthy subjects ¿age 50 (25, 59) years [median (range)], body mass index 23.1 (20.8, 25.5) kg.m(-2)¿ were investigated with three 2 h hyperinsulinaemic (60 micromol.l(-1))-euglycaemic (4.5 mmol.l(-1)) clamps performed 48 h and 14 days apart respectively. The third clamp was prolonged to 8 h in order to examine effects on glucose disposal during prolonged clamps. The glucose infusion rates (GIRs) during the three 2 h clamps were 7.41 (4.28, 10.96), 7.26 (5.38, 11. 02) and 6.63 (4.42, 10.3) mg.kg(-1).min(-1), with a median intra-individual coefficient of variation of 5.8 (2.6, 22) %. During the 8 h clamp a highly variable gradual increase in GIR was observed, reaching a plateau between 4 and 5 h at 32 (5, 101) % above the GIR between 1 and 2 h (P<0.05). This increase was correlated inversely with the GIR between 1 and 2 h (r=-0.82; P<0.05), and directly with age (r=0.86; P<0.05). Carbohydrate oxidation measured by indirect calorimetry was stable during the repeated 2 h clamps and the 8 h clamp. Endogenous glucose production measured by infusion of [6, 6-(2)H(2)]glucose was suppressed during the 8 h clamp. The 2 h hyperinsulinaemic-euglycaemic clamp is reproducible at a mid-physiological range of hyperinsulinaemia. If prolonged, it results in a delayed increase in non-oxidative glucose disposal, which is most pronounced in subjects with low insulin sensitivity. The findings underline the importance of selecting age-matched controls in studies of insulin resistance.

  10. ANTIBIOTIC PROPHYLAXIS IN BARIATRIC SURGERY: a continuous infusion of cefazolin versus ampicillin/sulbactam and ertapenem.

    PubMed

    Ferraz, Álvaro Antônio Bandeira; Siqueira, Luciana Teixeira de; Campos, Josemberg Marins; Araújo, Guido Correa de; Martins Filho, Euclides Dias; Ferraz, Edmundo Machado

    2015-01-01

    The incidence of surgical site infection in bariatric patients is significant and the current recommendations for antibiotic prophylaxis are sometimes inadequate. Objective: The aim of this study was to analyze the effect of three prophylactic antibiotic regimens on the incidence of surgical site infection. A prospective, cross-sectional study was conducted between January 2009 and January 2013 in which 896 Roux-en-Y gastric bypasses were performed to treat obesity. The study compared three groups of patients according to the perioperative antibiotic prophylaxis administered intravenously and beginning at anesthesia induction: Group I consisting of 194 patients treated with two 3-g doses of ampicillin/sulbactam; Group II with 303 patients treated with a single 1-g dose of ertapenem; and Group III with 399 patients treated with a 2-g dose of cefazolin at anesthesia induction followed by a continuous infusion of cefazolin 1g throughout the surgical procedure. The rate of surgical site infection was analyzed, as well as its association with age, sex, preoperative weight, body mass index and comorbidities. The rates of surgical site infection were 4.16% in the group treated prophylactically with ampicillin/sulbactam, 1.98% in the ertapenem group and 1.55% in the continuous cefazolin group. The prophylactic use of continuous cefazolin in surgeries for morbid obesity shows very promising results. These findings suggest that some prophylactic regimens need to be reconsidered and even substituted by more effective therapies for the prevention of surgical site infections in bariatric patients.

  11. Effect of glucose-insulin-potassium infusion on mortality in critical care settings: a systematic review and meta-analysis.

    PubMed

    Puskarich, Michael A; Runyon, Michael S; Trzeciak, Stephen; Kline, Jeffrey A; Jones, Alan E

    2009-07-01

    This study seeks to measure the treatment effect of glucose-insulin-potassium (GIK) infusion on mortality in critically ill patients. A systematic review of randomized controlled trials is conducted, comparing GIK treatment with standard care or placebo in critically ill adult patients. The primary outcome variable is mortality. Two authors independently extract data and assess study quality. The primary analysis is based on the random effects model to produce pooled odds ratios (ORs) with 95% confidence intervals (CIs). The search yields 1720 potential publications; 23 studies are included in the final analysis, providing a sample of 22,525 patients. The combined results demonstrate no heterogeneity (P=.57, I2=0%) and no effect on mortality (OR=1.02; 95% CI, 0.93-1.11) with GIK treatment. No experimental studies of shock or sepsis populations are identified. This meta-analysis finds that there is no mortality benefit to GIK infusion in critically ill patients; however, study populations are limited to acute myocardial infarction and cardiovascular surgery patients. No studies are identified using GIK in patients with septic shock or other forms of circulatory shock, providing an absence of evidence regarding the effect of GIK as a therapy in patients with shock.

  12. A web-based study of the relationship of duration of insulin pump infusion set use and fasting blood glucose level in adults with type 1 diabetes.

    PubMed

    Sampson Perrin, Alysa J; Guzzetta, Russell C; Miller, Kellee M; Foster, Nicole C; Lee, Anna; Lee, Joyce M; Block, Jennifer M; Beck, Roy W

    2015-05-01

    To evaluate the impact of infusion set use duration on glycemic control, we conducted an Internet-based study using the T1D Exchange's online patient community, Glu ( myGlu.org ). For 14 days, 243 electronically consented adults with type 1 diabetes (T1D) entered online that day's fasting blood glucose (FBG) level, the prior day's total daily insulin (TDI) dose, and whether the infusion set was changed. Mean duration of infusion set use was 3.0 days. Mean FBG level was higher with each successive day of infusion set use, increasing from 126 mg/dL on Day 1 to 133 mg/dL on Day 3 to 147 mg/dL on Day 5 (P<0.001). TDI dose did not vary with increased duration of infusion set use. Internet-based data collection was used to rapidly conduct the study at low cost. The results indicate that FBG levels increase with each additional day of insulin pump infusion set use.

  13. The effect of continuous subcutaneous recombinant PTH (1-34) infusion during pregnancy on calcium homeostasis - a case report.

    PubMed

    Ilany, Jacob; Vered, Iris; Cohen, Ohad

    2013-09-01

    We describe calcium homeostasis during pregestation and gestation in a woman with iatrogenic hypoparathyroidism, treated with continuous subcutaneous recombinant parathyroid hormone (PTH) (1-34) infusion. The requirement for PTH did not fluctuate much during pregnancy and was essential for maintaining normal calcium and phosphorus serum levels. This study documents the insufficiency of PTH-related protein (PTHrP) or other gestation-related hormones to compensate for PTH deficiency in hypoparathyroid women, and the successful utilization of continuous subcutaneous recombinant PTH (1-34) infusion to achieve normal calcium homeostasis during gestation. Clinical trials with PTH replacement in such circumstances are warranted.

  14. The effect of continuous low dose methylprednisolone infusion on inflammatory parameters in patients undergoing coronary artery bypass graft surgery: a randomized-controlled clinical trial.

    PubMed

    Ghiasi, Abbas; Shafiee, Akbar; Salehi Omran, Abbas; Ghaffari-Marandi, Neda; Shirzad, Mahmood; Barkhordari, Khosro

    2015-01-01

    This trial was performed to determine if a continuous low-dose infusion of methylprednisolone is as effective as its bolus of high-dose in reducing inflammatory response. The study was single-center, double-blinded randomized clinical trial and performed in a surgical intensive care unit of an academic hospital. In this study, 72 consecutive patients undergoing elective coronary artery bypass grafting (CABG) were assigned to receive either a methylprednisolone loading dose (1mg/kg) followed by continuous infusion (2mg/Kg/24 hours for 1 day) (low-dose regime) or a single dose of methylprednisolone (15 mg/kg) before cardiopulmonary bypass (high dose regime). Serum concentrations of IL-6 and C- reactive protein (CRP) were measured preoperatively and 6, 24 and 48 hours after surgery, and serum creatinine was measured before the operation and 24, 48 and 72 hours postoperatively. The measurements were then compared between the groups to evaluate the efficacy of each regimen. The basic characteristics and measurements were not different between the study groups. There was no significant difference in IL-6 and CRP elevation (P=0.52 and P=0.46, respectively). Early outcomes such as the length of stay in the intensive care unit, intubation time, changes in serum creatinine and blood glucose levels, inotropic support, insulin requirements, and rate of infection were also similar in both groups. A continuous low dose infusion of methylprednisolone was as effective as a single high dose methylprednisolone in reducing the inflammatory response after CABG with extracorporeal circulation with no significant difference in the postoperative measurements and outcomes.

  15. First Clinical Experience with a High-Capacity Implantable Infusion Pump for Continuous Intravenous Chemotherapy

    SciTech Connect

    Damascelli, Bruno; Patelli, Gianluigi; Frigerio, Laura F.; Lanocita, Rodolfo; Di Tolla, Giuseppe; Marchiano, Alfonso; Spreafico, Carlo; Garbagnati, Francesco; Bonalumi, Maria G.; Monfardini, Lorenzo; Ticha, Vladimira; Prino, Aurelio

    1999-01-15

    Purpose: To evaluate the efficiency of a new high-capacity pump for systemic venous chemotherapy and to verify the quality of implantation by interventional radiology staff. Methods: A total of 47 infusion pumps with a 60-ml reservoir and variable flow rates (2, 6, 8, or 12 ml/24 hr) were implanted by radiologists in 46 patients with solid tumor metastases requiring treatment with a single, continuously infused cytostatic agent. The reservoir was refilled transcutaneously, usually once weekly. The flow accuracy of the pump was assessed from actual drug delivery recorded on 34 patients over a minimum observation period of 180 days. Results: No early complications occurred in any of the 47 implants in 46 patients. A total of 12 (25.53%) complications occurred between 3 and 24 months after implantation. Seven (14.90%) of these were due to the external design of the pump, while five (10.63%) were related to the central venous catheter. In the 34 patients available for pump evaluation (follow-up of at least 180 days), the system was used for a total of 14,191 days (range 180-911 days, mean 417.38 days), giving an overall complication rate of 0.84 per 1000 days of operation. The mean flow rate accuracy was 90.26%. Conclusion: The new implantable pump showed good flow rate accuracy and reliable operation. The pump-related complications were related to its external design and have now been corrected by appropriate modifications. From a radiologic and surgical viewpoint, the venous implantation procedure is identical to that of conventional vascular access devices and can be performed by radiologists familiar with these techniques. The current limitations lie in the high cost of the pump and, for certain drugs, the short time between refills.

  16. A low dose euglycemic infusion of recombinant human insulin-like growth factor I rapidly suppresses fasting-enhanced pulsatile growth hormone secretion in humans.

    PubMed Central

    Hartman, M L; Clayton, P E; Johnson, M L; Celniker, A; Perlman, A J; Alberti, K G; Thorner, M O

    1993-01-01

    To determine if insulin-like growth factor I (IGF-I) inhibits pulsatile growth hormone (GH) secretion in man, recombinant human IGF-I (rhIGF-I) was infused for 6 h at 10 micrograms.kg-1.h-1 during a euglycemic clamp in 10 normal men who were fasted for 32 h to enhance GH secretion. Saline alone was infused during an otherwise identical second admission as a control. As a result of rhIGF-I infusion, total and free IGF-I concentrations increased three- and fourfold, respectively. Mean GH concentrations fell from 6.3 +/- 1.6 to 0.59 +/- 0.07 micrograms/liter after 120 min. GH secretion rates, calculated by a deconvolution algorithm, decreased with a t 1/2 of 16.6 min and remained suppressed thereafter. Suppression of GH secretion rates occurred within 60 min when total and free IGF-I concentrations were 1.6-fold and 2-fold above baseline levels, respectively, and while glucose infusion rates were < 1 mumol.kg-1.min-1. During saline infusion, GH secretion rates remained elevated. Infusion of rhIGF-I decreased the mass of GH secreted per pulse by 84% (P < 0.01) and the number of detectable GH secretory pulses by 32% (P < 0.05). Plasma insulin and glucagon decreased to nearly undetectable levels after 60 min of rhIGF-I. Serum free fatty acids, beta-hydroxybutyrate, and acetoacetate were unaffected during the first 3 h of rhIGF-I but decreased thereafter to 52, 32, and 50% of levels observed during saline. We conclude that fasting-enhanced GH secretion is rapidly suppressed by a low-dose euglycemic infusion of rhIGF-I. This effect of rhIGF-I is likely mediated through IGF-I receptors independently of its insulin-like metabolic actions. PMID:8514857

  17. A phase I and pharmacokinetic study with 21-day continuous infusion of epirubicin.

    PubMed

    de Vries, E G; Greidanus, J; Mulder, N H; Nieweg, M B; Postmus, P E; Schipper, D L; Sleijfer, D T; Uges, D R; Willemse, P H

    1987-09-01

    A phase I study with continuous administration of epirubicin for 21 days using a venous access port and a portable pump was performed. The first dose step was 2 mg/m2/d for 21 days. Interval between courses was 3 weeks. Dose increment per step was 1 mg/m2/d. Twenty-two patients entered the study and received a total of 58 courses with a median of two (range, one to nine). Up to 5 mg/m2/d no toxicity (according to World Health Organization [WHO] criteria) occurred. At 6 mg/m2/d (six pts), one patient had leukopenia grade 3. Two others had some hair loss. At 7 mg/m2/d (four patients), all patients developed mucositis (two grade 3). Three patients had bone marrow depression (one grade 3 anemia, one grade 4 leukocytopenia), and one patient developed the hand-foot syndrome. No other toxicity occurred in the patients. One patient obtained a partial response (18 weeks), ten had stable disease (12 to 54 weeks), seven had progressive disease, and four were not evaluable for response. One patient developed cellulitis around the port, responding to antibiotic treatment; one patient developed a vena cava superior syndrome that resolved with urokinase and removal of the access port. No septicemia occurred. Pharmacokinetic studies were performed by high-performance liquid chromatography (HPLC) with fluorometric detection. Plasma steady state was reached after 57 hours. During steady state there was a linear relationship between epirubicin dose administered and epirubicin level in plasma (r = .58, P less than .05), whole blood (r = .75, P less than .005), and in leukocytes (r = .68, P less than .05). The area under the curve in leukocytes was higher with continuous infusion of 6 mg/m2 for 21 days compared with bolus injection of 80 mg/m2. This method of continuous infusion with epirubicin may be a way to increase intracellular drug-uptake as expressed by intracellular area under curve (AUC). We recommend 6 mg/m2/d for 3 weeks for evaluation of antitumor efficacy in phase II

  18. Amino acid infusion increases the sensitivity of muscle protein synthesis in vivo to insulin. Effect of branched-chain amino acids.

    PubMed Central

    Garlick, P J; Grant, I

    1988-01-01

    Rates of muscle protein synthesis were measured in vivo in tissues of post-absorptive young rats that were given intravenous infusions of various combinations of insulin and amino acids. In the absence of amino acid infusion, there was a steady rise in muscle protein synthesis with plasma insulin concentration up to 158 mu units/ml, but when a complete amino acids mixtures was included maximal rates were obtained at 20 mu units/ml. The effect of the complete mixture could be reproduced by a mixture of essential amino acids or of branched-chain amino acids, but not by a non-essential mixture, alanine, methionine or glutamine. It is concluded that amino acids, particularly the branched-chain ones, increase the sensitivity of muscle protein synthesis to insulin. PMID:3052439

  19. Wearable near-infrared optical probe for continuous monitoring during breast cancer neoadjuvant chemotherapy infusions

    NASA Astrophysics Data System (ADS)

    Teng, Fei; Cormier, Timothy; Sauer-Budge, Alexis; Chaudhury, Rachita; Pera, Vivian; Istfan, Raeef; Chargin, David; Brookfield, Samuel; Ko, Naomi Yu; Roblyer, Darren M.

    2017-01-01

    We present a new continuous-wave wearable diffuse optical probe aimed at investigating the hemodynamic response of locally advanced breast cancer patients during neoadjuvant chemotherapy infusions. The system consists of a flexible printed circuit board that supports an array of six dual wavelength surface-mount LED and photodiode pairs. The probe is encased in a soft silicone housing that conforms to natural breast shape. Probe performance was evaluated using tissue-simulating phantoms and in vivo normal volunteer measurements. High SNR (71 dB), low source-detector crosstalk (-60 dB), high measurement precision (0.17%), and good thermal stability (0.22% Vrms/°C) were achieved in phantom studies. A cuff occlusion experiment was performed on the forearm of a healthy volunteer to demonstrate the ability to track rapid hemodynamic changes. Proof-of-principle normal volunteer measurements were taken to demonstrate the ability to collect continuous in vivo breast measurements. This wearable probe is a first of its kind tool to explore prognostic hemodynamic changes during chemotherapy in breast cancer patients.

  20. [Current concept of insulin therapy intensification, and the role of human regular insulin and rapid-acting insulin analogs in insulin treatment].

    PubMed

    Hamaguchi, Tomoya; Sadahiro, Katsuhiko; Satoh, Tomomi

    2015-03-01

    The evolution of insulin therapy from animal insulin to recombinant human regular insulin has improved diabetes treatment. Generating of rapid-acting insulin analogs, mimicking physiologic insulin action enables us to provide better control of post-prandial glucose level and lower incidence of hypoglycemia compared with human regular insulin. These rapid-acting insulin analogs show lower susceptibility of insulin precipitation and catheter occlusions, and are suitable for insulin pump therapy of continuous subcutaneous insulin infusion. Insulin lispro and insulin aspart are also applicable for diabetic patients with pregnancy, requiring excellent glycemic control. In some studies, stepwise addition of prandial insulin, as well as full basal-bolus regimen can improve glycemic control with less hypoglycemia. Treatment intensification with rapid-acting insulin analogs may offer a proper method to reach glycemic goals.

  1. Effectiveness of continuous wound infusion of local anesthetics after abdominal surgeries.

    PubMed

    Dhanapal, Baskaran; Sistla, Sarath Chandra; Badhe, Ashok Shankar; Ali, Sheikh Manwar; Ravichandran, Niranjan T; Galidevara, Indira

    2017-05-15

    To assess the effectiveness of continuous preperitoneal wound infusion of local anesthetic drug bupivacaine in providing pain relief, reducing opioid consumption, and enhancing postoperative recovery. Eligible patients were randomly allocated to two groups (study group: bupivacaine and control group: normal saline). There were 47 patients in each group. The patients received continuous infusion of either 0.25% bupivacaine or 0.9% normal saline at 6 mL/h, for 48 h, based on their group allocation, through a multiholed wound infiltration catheter placed preperitoneally. All patients also received intravenous morphine through patient-controlled analgesia pump. Pain scores at rest and on cough, morphine consumption, and peak expiratory flow rate were assessed at 12, 24, and 48 h postoperatively. The time to first perception of bowel sounds and first passage of flatus was noted. All patients were assessed for postoperative nausea and vomiting and any local or systemic complications. Chi-square test was used to compare categorical variables. The morphine consumption was compared using Student t-test, the visual analogue scale (VAS) scores were compared using repeated-measures analysis of variance. The mean total morphine consumption in the study group was significantly lower than the control group (18.8 ± 2.21 versus 30.8 ± 2.58 mg, P = 0.001). The median VAS scores were significantly lower in the study group than those in the control group both at rest (3 [1-4] versus 4 [2-5], P = 0.04) and during cough (4 [3-6] versus 6 [4-6] P = 0.03), except at 48 h, when the median VAS score at rest was similar (3 [1-4] versus 3 [2-4], P = 0.56). Bowel function returned earlier in study group (67.34 ± 2.61 versus 76.34 ± 5.29 h, P = 0.03). Postoperative nausea and vomiting was less in study group. Respiratory function, assessed by peak expiratory flow rate, was better in the study group (192.55 ± 12.93 versus 165.31 ± 9.32 mL, P = 0.03). The

  2. Effects of an overnight intravenous lipid infusion on intramyocellular lipid content and insulin sensitivity in African-American versus Caucasian adolescents

    PubMed Central

    Lee, SoJung; Boesch, Chris; Kuk, Jennifer L.; Arslanian, Silva

    2012-01-01

    Objective To explain the predisposition for insulin resistance among African American (AA) adolescents, this study aimed to: 1) examine changes in intramyocellular lipid content (IMCL), and insulin sensitivity with intralipid (IL) infusion; and 2) determine whether the increase in IMCL is comparable between AA and Caucasian adolescents. Materials and Methods Thirteen AA and 15 Caucasian normal-weight adolescents (BMI <85th) underwent a 3-h hyperinsulinemic-euglycemic clamp, on two occasions in random order, after an overnight 12-hr infusion of: 1) 20% IL and 2) normal saline (NS). IMCL was quantified by 1H-magnetic resonance spectroscopy in tibialis anterior muscle before and after IL infusion. Results During IL infusion, plasma TG, glycerol, FFA and fat oxidation increased significantly, with no race differences. Hepatic insulin sensitivity decreased with IL infusion with no difference between the groups. IL infusion was associated with a significant increase in IMCL, which was comparable between AA (Δ 105%; NS: 1.9 ± 0.8 vs. IL: 3.9 ± 1.6 mmol/kg wet weight) and Caucasian (Δ 86%; NS: 2.8 ± 2.1 vs. IL: 5.2 ± 2.4 mmol/kg wet weight), with similar reductions (P<0.01) in insulin sensitivity between the groups (Δ −44%: NS: 9.1 ± 3.3 vs. IL: 5.1 ± 1.8 mg/kg/min per µU/ml in AA) and (Δ−39%: NS: 12.9 ± 6.0 vs. IL: 7.9 ± 3.8 mg/kg/min per µU/ml in Caucasian) adolescents. Conclusions In healthy adolescents, an acute elevation in plasma FFA with IL infusion is accompanied by significant increases in IMCL and reductions in insulin sensitivity with no race differential. Our findings suggest that AA normal-weight adolescents are not more susceptible than Caucasians to FFA-induced IMCL accumulation and insulin resistance. PMID:23122836

  3. Continuous intra-articular infusion anesthesia for pain control after total knee arthroplasty: study protocol for a randomized controlled trial

    PubMed Central

    2014-01-01

    Background Postoperative pain control after total knee arthroplasty (TKA) remains a great challenge. The management of pain in the immediate postoperative period is one of the most critical aspects to allow speedier rehabilitation and reduce the risk of postoperative complications. Recently, periarticular infiltration anesthesia has become popular, but the outcome is controversial. Some studies have shown transient effects, “rebound pain”, or no effectiveness in pain control. Continuous intra-articular infusion technique has been introduced to improve these transient effects, but more clinical studies are needed. Furthermore, the potential risk of early periprosthetic joint infection is causing concerning. We plan to compare continuous intra-articular infusion anesthesia with epidural infusion anesthesia after TKA to assess the effectiveness of this technique in reducing pain, in improving postoperative function, and to look at the evidence for risk of early infection. Methods/design This trial is a randomized, controlled study. Patients (n = 214) will be randomized into two groups: to receive continuous intra-articular infusion anesthesia (group C); and epidural infusion anesthesia (group E). For the first 3 postoperative days, pain at rest, active range of motion (A-ROM), rescue analgesia and side effects will be recorded. At 3-month and 6-month follow-up, A-ROM, C-reactive protein, erythrocyte sedimentation rate, and synovial fluid cell count and culture will be analyzed. Discussion The results from this study will provide clinical evidence on the efficacy of a continuous intra-articular infusion technique in reducing pain, postoperative functional improvement and safety. It will be the first randomized controlled trial to investigate infection risk with local anesthesia after TKA. Trial registration ClinicalTrials.gov identifier: ChiCTR-TRC-13003999 PMID:24958315

  4. Efficacy of different doses of sugammadex after continuous infusion of rocuronium

    PubMed Central

    Soto Mesa, Diego; Fayad Fayad, Mounir; Pérez Arviza, Laura; Del Valle Ruiz, Verónica; Cosío Carreño, Fernando; Arguelles Tamargo, Luis; Amorín Díaz, Manuel; Fernández-Pello Montes, Sergio

    2015-01-01

    AIM: To evaluate the effects of two different doses of sugammadex after maintenance anesthesia with sevofluorane and remifentanil and deep rocuronium-induced neuromuscular blockade (NMB). METHODS: Patients between 20 and 65 years of age, with American Society of Anesthesiologists physical status classification I-II, undergoing gynecological surgery were included in a prospective, comparative and randomized study. NMB was induced with an injection of 0.6 mg/kg of rocuronium followed by continuous infusion of 0.3-0.6 mg/kg per hour to maintain a deep block. Anesthesia was maintained with sevofluorane and remifentanil. Finally, when surgery was finished, a bolus of 2 mg/kg (group A) or 4 mg/kg (group B) of sugammadex was applied when the NMB first response in the train-of-four was reached. The primary clinical endpoint was time to recovery to a train-of-four ratio of 0.9. Other variables recorded were the time until recovery of train-of-four ratio of 0.7, 0.8, hemodynamic variables (arterial blood pressure and heart rate at baseline, starting sugammadex, and minutes 2, 5 and 10) and adverse events were presented after one hour in the post-anesthesia care unit. RESULTS: Thirty-two patients were included in the study: 16 patients in group A and 16 patients in group B. Only 14 patients each group were recorded because arterial pressure values were lost in two patients from each group in minute 10. The two groups were comparable. Median recovery time from starting of sugammadex administration to a train-of-four ratio of 0.9 in group A and B was 129 and 110 s, respectively. The estimated difference in recovery time between groups was 24 s (95%CI: 0 to 45 s, Hodges-Lehmann estimator), entirely within the predefined equivalence interval. Times to recovery to train-of-four ratios of 0.8 (group A: 101 s; group B: 82.5 s) and 0.7 (group A: 90 s; group B: 65 s) from start of sugammadex administration were not equivalent between groups. There was not a significant variation in

  5. Efficacy of different doses of sugammadex after continuous infusion of rocuronium.

    PubMed

    Soto Mesa, Diego; Fayad Fayad, Mounir; Pérez Arviza, Laura; Del Valle Ruiz, Verónica; Cosío Carreño, Fernando; Arguelles Tamargo, Luis; Amorín Díaz, Manuel; Fernández-Pello Montes, Sergio

    2015-04-16

    To evaluate the effects of two different doses of sugammadex after maintenance anesthesia with sevofluorane and remifentanil and deep rocuronium-induced neuromuscular blockade (NMB). Patients between 20 and 65 years of age, with American Society of Anesthesiologists physical status classification I-II, undergoing gynecological surgery were included in a prospective, comparative and randomized study. NMB was induced with an injection of 0.6 mg/kg of rocuronium followed by continuous infusion of 0.3-0.6 mg/kg per hour to maintain a deep block. Anesthesia was maintained with sevofluorane and remifentanil. Finally, when surgery was finished, a bolus of 2 mg/kg (group A) or 4 mg/kg (group B) of sugammadex was applied when the NMB first response in the train-of-four was reached. The primary clinical endpoint was time to recovery to a train-of-four ratio of 0.9. Other variables recorded were the time until recovery of train-of-four ratio of 0.7, 0.8, hemodynamic variables (arterial blood pressure and heart rate at baseline, starting sugammadex, and minutes 2, 5 and 10) and adverse events were presented after one hour in the post-anesthesia care unit. Thirty-two patients were included in the study: 16 patients in group A and 16 patients in group B. Only 14 patients each group were recorded because arterial pressure values were lost in two patients from each group in minute 10. The two groups were comparable. Median recovery time from starting of sugammadex administration to a train-of-four ratio of 0.9 in group A and B was 129 and 110 s, respectively. The estimated difference in recovery time between groups was 24 s (95%CI: 0 to 45 s, Hodges-Lehmann estimator), entirely within the predefined equivalence interval. Times to recovery to train-of-four ratios of 0.8 (group A: 101 s; group B: 82.5 s) and 0.7 (group A: 90 s; group B: 65 s) from start of sugammadex administration were not equivalent between groups. There was not a significant variation in the arterial pressure

  6. Intraperitoneal Continuous-Rate Infusion for the Maintenance of Anesthesia in Laboratory Mice (Mus musculus)

    PubMed Central

    Erickson, Rebecca L; Terzi, Matthew C; Jaber, Samer M; Hankenson, F Claire; McKinstry-Wu, Andrew; Kelz, Max B; Marx, James O

    2016-01-01

    Intraperitoneal injectable anesthetics are often used to achieve surgical anesthesia in laboratory mice. Because bolus redosing of injectable anesthetics can cause unacceptably high mortality, we evaluated intraperitoneal continuous-rate infusion (CRI) of ketamine with or without xylazine for maintaining surgical anesthesia for an extended period of time. Anesthesia was induced in male C57BL/6J mice by using ketamine (80 mg/kg) and xylazine (8 mg/kg) without or with acepromazine at 0.1 mg/kg or 0.5 mg/kg. At 10 min after induction, CRI for 90 min was initiated and comprised 25%, 50%, or 100% of the initial ketamine dose per hour or 50% of the initial doses of both ketamine and xylazine. Anesthetic regimens were compared on the basis of animal immobility, continuous surgical depth of anesthesia as determined by the absence of a pedal withdrawal reflex, and mortality. Consistent with previous studies, the response to anesthetics was highly variable. Regimens that provided the longest continuous surgical plane of anesthesia with minimal mortality were ketamine–xylazine–acepromazine (0.1 mg/kg) with CRI of 100% of the initial ketamine dose and ketamine–xylazine–acepromazine (0.5 mg/kg) with CRI of 50% of the initial ketamine and xylazine doses. In addition, heart rate and respiratory rate did not increase consistently in response to a noxious stimulus during CRI anesthesia, even when mice exhibited a positive pedal withdrawal reflex, suggesting that these parameters are unreliable indicators of anesthetic depth during ketamine–xylazine anesthesia in mice. We conclude that intraperitoneal CRI anesthesia in mice prolongs injectable anesthesia more consistently and with lower mortality than does bolus redosing. PMID:27657709

  7. Characterization of a model of systemic inflammation in humans in vivo elicited by continuous infusion of endotoxin

    PubMed Central

    Kiers, D.; Koch, R. M.; Hamers, L.; Gerretsen, J.; Thijs, E. J. M.; van Ede, L.; Riksen, N. P.; Kox, M.; Pickkers, P.

    2017-01-01

    Investigating the systemic inflammatory response in patients with critical illness such as sepsis, trauma and burns is complicated due to uncertainties about the onset, duration and severity of the insult. Therefore, in vivo models of inflammation are essential to study the pathophysiology and to evaluate immunomodulatory therapies. Intravenous bolus administration of endotoxin to healthy volunteers is a well-established model of a short-lived systemic inflammatory response, characterized by increased plasma cytokine levels, flu-like symptoms and fever. In contrast, patients suffering from systemic inflammation are often exposed to inflammatory stimuli for an extended period of time. Therefore, continuous infusion of endotoxin may better reflect the kinetics of the inflammatory response encountered in these patients. Herein, we characterize a novel model of systemic inflammation elicited by a bolus infusion of 1 ng/kg, followed by a 3hr continuous infusion of 1 ng/kg/h of endotoxin in healthy volunteers, and compared it with models of bolus administrations of 1 and 2 ng/kg of endotoxin. The novel model was well-tolerated and resulted in a more pronounced increase in plasma cytokine levels with different kinetics and more prolonged symptoms and fever compared with the bolus-only models. Therefore, the continuous endotoxin infusion model provides novel insights into kinetics of the inflammatory response during continuous inflammatory stimuli and accommodates a larger time window to evaluate immunomodulating therapies. PMID:28054645

  8. Regular intermittent bolus provides similar incidence of maternal fever compared with continuous infusion during epidural labor analgesia

    PubMed Central

    Feng, Shan-Wu; Xu, Shi-Qin; Ma, Li; Li, Cai-Juan; Wang, Xian; Yuan, Hong-Mei; Wang, Fu-Zhou; Shen, Xiao-Feng; Ding, Zheng-Nian

    2014-01-01

    Objectives: To compare the effects of regular intermittent bolus versus continuous infusion for epidural labor analgesia on maternal temperature and serum interleukin-6 (IL-6) level. Methods: This randomized trial was performed in Nanjing Maternity and Child Health Care Hospital, Nanjing, Jiangsu Province, China between October 2012 and February 2014. Either regular intermittent bolus (RIB, n=66) or continuous infusion (CI, n=66) was used for epidural labor analgesia. A bolus dose (10 ml of 0.08% ropivacaine + 0.4 µg·ml-1 sufentanil) was manually administrated once an hour in the RIB group, whereas the same solution was continuously infused at a constant rate of 10 ml·h-1 in the CI group. Maternal tympanic temperature and serum IL-6 level were measured hourly from baseline to one hour post partum. The incidences of fever (≥38ºC) were calculated. Results: The incidence of maternal fever was similar between the 2 groups. There was a rising trend in mean temperature over time in both groups, but no statistical difference was detected between the groups at respective time points; maternal serum IL-6 showed similar changes. Conclusion: Compared with continuous infusion, regular intermittent bolus presents with the same incidence of maternal fever for epidural labor analgesia. Interleukin-6 elevation could be involved in mean maternal temperature increase. PMID:25316469

  9. Controlled Study of the Effects of Continuous Intrathecal Baclofen Infusion in Non-Ambulant Children with Cerebral Palsy

    ERIC Educational Resources Information Center

    Morton, Richard E.; Gray, Natalie; Vloeberghs, Michael

    2011-01-01

    Aim: To measure changes in children with severe spastic cerebral palsy (CP) after continuous intrathecal baclofen (ITB) infusion over 18 months and to compare the results with those of a comparison group awaiting treatment. Method: Thirty-eight children with severe spastic CP considered suitable for ITB were assessed when first seen, just before…

  10. Comparison of the Pharmacokinetics of Ketorolac Tromethamine After Continuous Subcutaneous Infusion and Repeat Intramuscular Bolus Injections in Healthy Adult Subjects.

    PubMed

    Burdick, Michael; Mamelok, Richard; Hurliman, Michele; Dupuis, Mariève; Xie, Yuli; Grenier, Julie; Sheldon, Curtis; Gartner, Michael; Noymer, Peter

    2017-07-01

    Ketorolac tromethamine is a nonsteroidal anti-inflammatory drug that exhibits analgesic activity with no sedative or anxiolytic properties. Twelve healthy male subjects were enrolled in a study to receive either of 2 treatments over 2 periods in an open-label, randomized, 2-way crossover design: (A) 120 mg of ketorolac tromethamine administered as a continuous subcutaneous infusion over a 24-hour period; or (B) an identical total daily dose administered as 4 intramuscular bolus injections of 30 mg each given every 6 hours (current labeled treatment regimen). The pharmacokinetic and safety profiles were evaluated for both treatments. Both modes of administration have similar values for area under the curve (AUC) and half-life (t1/2 ), suggesting that continuous subcutaneous infusion and repeated intramuscular bolus injections have similar bioavailability. The peak plasma concentration (Cmax ) was 40% lower when ketorolac was administered as a continuous subcutaneous infusion compared with repeat intramuscular bolus injections. The concentration at steady-state (Css ) for continuous subcutaneous infusion was between the Cmax and Ctrough values obtained following the 4 intramuscular injections. Both treatment arms were well tolerated. © 2016, The American College of Clinical Pharmacology.

  11. Regular intermittent bolus provides similar incidence of maternal fever compared with continuous infusion during epidural labor analgesia.

    PubMed

    Feng, Shan-Wu; Xu, Shi-Qin; Ma, Li; Li, Cai-Juan; Wang, Xian; Yuan, Hong-Mei; Wang, Fu-Zhou; Shen, Xiao-Feng; Ding, Zheng-Nian

    2014-10-01

    To compare the effects of regular intermittent bolus versus continuous infusion for epidural labor analgesia on maternal temperature and serum interleukin-6 (IL-6) level. This randomized trial was performed in Nanjing Maternity and Child Health Care Hospital, Nanjing, Jiangsu Province, China between October 2012 and February 2014. Either regular intermittent bolus (RIB, n=66) or continuous infusion (CI, n=66) was used for epidural labor analgesia. A bolus dose (10 ml of 0.08% ropivacaine + 0.4 ug·ml-1 sufentanil) was manually administrated once an hour in the RIB group, whereas the same solution was continuously infused at a constant rate of 10 ml·h-1 in the CI group. Maternal tympanic temperature and serum IL-6 level were measured hourly from baseline to one hour post partum. The incidences of fever (>/=38 degree celsius ) were calculated. The incidence of maternal fever was similar between the 2 groups. There was a rising trend in mean temperature over time in both groups, but no statistical difference was detected between the groups at respective time points; maternal serum IL-6 showed similar changes. Compared with continuous infusion, regular intermittent bolus presents with the same incidence of maternal fever for epidural labor analgesia. Interleukin-6 elevation could be involved in mean maternal temperature increase. 

  12. Controlled Study of the Effects of Continuous Intrathecal Baclofen Infusion in Non-Ambulant Children with Cerebral Palsy

    ERIC Educational Resources Information Center

    Morton, Richard E.; Gray, Natalie; Vloeberghs, Michael

    2011-01-01

    Aim: To measure changes in children with severe spastic cerebral palsy (CP) after continuous intrathecal baclofen (ITB) infusion over 18 months and to compare the results with those of a comparison group awaiting treatment. Method: Thirty-eight children with severe spastic CP considered suitable for ITB were assessed when first seen, just before…

  13. Effects of continuous glucocorticoid infusion on the progression of dentinal caries in growing rats.

    PubMed

    Huumonen, S; Larmas, M

    1998-10-01

    This study was undertaken to test the effects of a low dose of continuous glucocorticoid infusion on the rate of progression of dentinal caries in molars of young rats. Forty-seven rats were inoculated in the mouth with Streptococcus sobrinus and fed ad libitum a cariogenic diet and 10% sweetened water. After 10 days of caries initiation ten animals were killed to serve as a reference group. In the rest of the animals the cortisone or placebo pellet was implanted subcutaneously in the back of the neck. The daily release of cortisone was 0.42 mg per rat. Sweetened water was changed to pure water, and the diet was the same cariogenic diet. After 6 weeks of medication the areas of dentinal caries were quantified planimetrically. Schiff's staining was used to classify caries. Although cortisone medication slightly increased the number of carious lesions, statistical significance was not reached. However, compared with the placebo group, the rats receiving cortisone medication showed significantly increased dentinal caries progression and severity of lesions. This study suggests that glucocorticoids with a cariogenic diet reduce the intrinsic modulation or response of the odontoblasts to caries attack.

  14. A simulation of loading doses for vancomycin continuous infusion regimens in intensive care.

    PubMed

    Šíma, Martin; Hronová, Karolína; Hartinger, Jan; Slanař, Ondřej

    2017-09-01

    Delayed achievement of target vancomycin serum concentrations may adversely affect clinical outcomes. The objective of this retrospective study was to compare the prediction accuracy of different body weight descriptors for volume of distribution and to propose an optimal loading dose (LD) for continuous infusion regimens in adults. Pharmacokinetic variables were computed using one-compartmental analysis. Simulated LDs of vancomycin were evaluated for each patient. Volume of distribution, clearance, and half-life median values (interquartile range) for vancomycin in the study population (n = 30) were 0.45 (0.39-0.61) L.kg(-1), 0.026 (0.015-0.040) L.h(-1).kg(-1), and 10.3 (7.7-21.3) h, respectively. The observed volume of distribution was better predicted by total body weight (TBW) than by the ideal body weight or the adjusted body weight. An LD of 10.7 mg per kg TBW was optimal in our study population. Using this LD, 17.9% of simulated vancomycin serum levels were just below the therapeutic range, only 10.7% concentrations exceeded the target range and no concentration was toxic. The use of a LD would lead to reduced median time to reach target concentrations from 17 to 1 h.

  15. Continuous infusion of propofol or intermittent bolus of tiletamine-zolazepam in squirrel monkeys (Saimiri sciureus).

    PubMed

    Galante, Rafaela; Muniz, José A P C; Castro, Paulo H G; Gris, Vanessa N; Carvalho, Elizabeth R; Amora, Dorli S; Vilani, Ricardo G D'O C

    2014-09-01

    To investigate an infusion of propofol for anesthesia in comparison to tiletamine-zolazepam anesthesia, evaluating physiological variables and recovery in squirrel monkeys. Prospective non-blinded randomized study. Eight healthy squirrel monkeys (Saimiri sciureus), aged 3 years and weighing 0.340-0.695 kg. Premedication was intramuscular midazolam (0.5 mg) and meperidine (4 mg). Anesthesia was induced with intravenous (IV) propofol (4 mg kg(-1)  minute(-1) ) and maintained with propofol starting at 0.4 mg kg(-1)  minute(-1) (PRO, n = 4) or IV tiletamine-zolazepam (5 mg kg(-1) ) and maintained with supplementary doses of TZ (TZ, n = 4). Cardiopulmonary variables were measured continuously. Arterial blood gases and lactate concentration were measured at the end of anesthesia. Quality and times of recovery were determined. Repeatedly measured data for significant differences were tested between groups with t-test and within groups by anova. Median time for induction of anesthesia in PRO was 180 seconds. Mean maintenance infusion rate of propofol was 0.43 ± 0.05 mg kg(-1)  minute(-1) , varying during the 1 hour period. One monkey died after administration of TZ; others required 1, 4, or 8 supplemental doses. Cardiopulmonary variables were similar between groups, but hypotension was recorded. Recovery times to ventral recumbency in PRO (32 ± 17 minutes) and TZ (84 ± 11 minutes) and normal ambulation in PRO (58 ± 22 minutes) and TZ (358 ± 109minutes) were significantly different (p < 0.05). Recovery quality was superior in PRO, with less ataxia and fewer unsuccessful attempts to stand. Lactate concentration was not different between treatments. Cardiopulmonary variables were similar between protocols, aside from the higher incidence of hypotension in PRO, indicating that further studies with a larger number of animals are required. Compared to tiletamine-zolazepam, propofol anesthesia provided faster and superior anesthetic

  16. Continuous versus intermittent infusion of cefepime in neurosurgical patients with post-operative intracranial infections.

    PubMed

    Huang, Huawei; Huang, Shengyue; Zhu, Pengli; Xi, Xiuming

    2014-01-01

    Cefepime is administered as an intermittent infusion (II); however, continuous infusion (CI) may be advantageous because β-lactam antibiotics exhibit time-dependent antibacterial activity. This retrospective, non-randomised, comparative study included 68 neurosurgical patients with post-operative intracranial infections treated with 4g/day cefepime over 24h as a CI (n=34) or 2g every 12h as II (n=34). CI controlled the intracranial infection more rapidly and effectively than II (6.6±1.9 days vs. 7.8±2.6 days; P=0.036). By considering the minimum inhibitory concentrations (MICs) to be 4μg/mL and 8μg/mL, the percentage of time when the cefepime plasma or CSF concentrations were higher than the MIC (%T>MIC) was calculated for each patient. For plasma cefepime concentrations, the %T(>MIC) in the CI group was higher than in the II group (for MICs of 8μg/mL, 100% vs. 75%, respectively). The mean calculated area under the curve (AUC) in the CI group was similar to the II group (1197.99±72.15μgh/mL vs. 890.84±140.78μgh/mL; P=0.655). For CSF cefepime concentrations, the %T(>MIC) in the CI group was higher than in the II group (for MICs of 4μg/mL and 8μg/mL, 83.3% and 75% vs. 25% and 0%, respectively). The mean calculated AUC for the CI group was higher than the II group (220.56±13.59μgh/mL vs. 86.34±5.69μgh/mL; P=0.003). Therefore, CI of cefepime significantly enhanced the antibacterial effect and reduced the treatment duration in neurosurgical patients with post-operative intracranial infections.

  17. New Regimen for Continuous Infusion of Vancomycin in Critically Ill Patients

    PubMed Central

    Cristallini, Stefano; Hites, Maya; Kabtouri, Hakim; Roberts, Jason A.; Beumier, Marjorie; Cotton, Frederic; Lipman, Jeffrey; Jacobs, Frédérique; Vincent, Jean-Louis; Creteur, Jacques

    2016-01-01

    Despite the development of new agents with activity against Gram-positive bacteria, vancomycin remains one of the primary antibiotics for critically ill septic patients. Because sepsis can alter antimicrobial pharmacokinetics, the development of an appropriate dosing strategy to provide adequate concentrations is crucial. The aim of this study was to prospectively validate a new dosing regimen of vancomycin given by continuous infusion (CI) to septic patients. We included all adult septic patients admitted to a mixed intensive care unit (ICU) between January 2012 and May 2013, who were treated with a new vancomycin CI regimen consisting of a loading dose of 35 mg/kg of body weight given as a 4-h infusion, followed by a daily CI dose adapted to creatinine clearance (CrCL), as estimated by the Cockcroft-Gault formula (median dose, 2,112 [1,500 to 2,838] mg). Vancomycin concentrations were measured at the end of the loading dose (T1), at 12 h (T2), at 24 h (T3), and the day after the start of therapy (T4). Vancomycin concentrations of 20 to 30 mg/liter at T2, T3, and T4 were considered adequate. A total of 107 patients (72% male) were included. Median age, weight, and CrCL were 59 (interquartile range [IQR], 48 to 71) years, 75 (IQR, 65 to 85) kg, and 94 (IQR, 56 to 140) ml/min, respectively. Vancomycin concentrations were 44 (IQR, 37 to 49), 25 (IQR, 21 to 32), 22 (IQR, 19 to 28), and 26 (IQR, 22 to 29) mg/liter at T1, T2, T3, and T4, respectively. Concentrations were adequate in 56% (60/107) of patients at T2, in 54% (57/105) at T3, and in 73% (41/56) at T4. This vancomycin regimen permitted rapid attainment of target concentrations in serum for most patients. Concentrations were insufficient in only 16% of patients at 12 h of treatment. PMID:27216073

  18. Infusion of long-chain fatty acid anions by continuous-flow centrifugation

    PubMed Central

    Greenough, William B.; Crespin, Stephen R.; Steinberg, Daniel

    1969-01-01

    We have developed a method for the rapid infusion into plasma of large amounts of long-chain free fatty acids (FFA). Unanesthetized dogs were connected by a peripheral artery to a closed, continuousflow centrifuge from which cells and plasma emerged in separate lines. Sodium oleate was infused directly into the plasma line before cells and plasma were recombined and returned to the animal through a peripheral vein. The centrifugation procedure itself produced only small changes in circulating levels of glucose, FFA, and electrolytes. Plasma flow rates as high as 100 ml/min could be maintained, and centrifugations of 12 hr were accomplished without complications. During centrifugation, sodium oleate was infused at rates up to 80 μEq/kg per min for 2.5 hr; the maximum molar ratio of FFA to albumin without hemolysis was 10:1. Plasma FFA levels rose rapidly after infusions were started and reached constant elevated levels within 15-20 min. Oleate infusion at 10-50 μEq/kg per min produced a rise in plasma FFA proportional to the infusion rate. The maximum increment in plasma FFA above control values was 1.66 μEq/ml. When infusions ended, plasma FFA declined rapidly to control levels. Oleate infusion at rates below 30 μEq/kg per min did not reduce levels of other plasma FFA. Infusion at high rates was accompanied by a marked fall in blood glucose. This method permits adminsitration of long-chain fatty acids in sufficient quantities to study their individual metabolic effects, and provides a new way to supply lipid calories parenterally. PMID:5822596

  19. Baseline albumin is associated with worsening renal function in patients with acute decompensated heart failure receiving continuous infusion loop diuretics.

    PubMed

    Clarke, Megan M; Dorsch, Michael P; Kim, Susie; Aaronson, Keith D; Koelling, Todd M; Bleske, Barry E

    2013-06-01

    To identify baseline predictors of worsening renal function (WRF) in an acute decompensated heart failure (ADHF) patient population receiving continuous infusion loop diuretics. Retrospective observational analysis. Academic tertiary medical center. A total of 177 patients with ADHF receiving continuous infusion loop diuretics from January 2006 through June 2009. The mean patient age was 61 years, 63% were male, ~45% were classified as New York Heart Association functional class III, and the median length of loop diuretic infusion was 4 days. Forty-eight patients (27%) developed WRF, and 34 patients (19%) died during hospitalization. Cox regression time-to-event analysis was used to determine the time to WRF based on different demographic and clinical variables. Baseline serum albumin 3 g/dl or less was the only significant predictor of WRF (hazard ratio [HR] 2.87, 95% confidence interval [CI] 1.60-5.16, p=0.0004), which remained significant despite adjustments for other covariates. Serum albumin 3 g/dl or less is a practical baseline characteristic associated with the development of WRF in patients with ADHF receiving continuous infusion loop diuretics. © 2013 Pharmacotherapy Publications, Inc.

  20. Comparison of continuous infusion with intermittent bolus administration of cefotaxime on blood and cavity fluid drug concentrations in neonatal foals.

    PubMed

    Hewson, J; Johnson, R; Arroyo, L G; Diaz-Mendez, A; Ruiz-López, J A; Gu, Y; del Castillo, J R E

    2013-02-01

    Healthy neonatal foals were treated with cefotaxime by bolus (40 mg/kg i.v. q6h for 12 doses; n=10) or by infusion (loading dose of 40 mg/kg i.v. followed by continuous infusion of a total daily dose of 160 mg/kg per 24 h for 3 days; n=5). Population pharmacokinetics was determined, and concentrations in cavity fluids were measured at steady state (72 h). Highest measured serum drug concentration in the bolus group was 88.09 μg/mL and minimum drug concentration (C(min)) was 0.78 μg/mL at 6-h postadministration (immediately before each next dose), whereas infusion resulted in a steady-state concentration of 16.10 μg/mL in the infusion group. Mean cefotaxime concentration in joint fluid at 72 h was higher (P=0.051) in the infusion group (5.02 μg/mL) compared to the bolus group (0.78 μg/mL). Drug concentration in CSF at 72 h was not different between groups (P=0.243) and was substantially lower than serum concentrations in either group. Insufficient data on pulmonary epithelial lining fluid were available to compare the methods of administration for cefotaxime in this cavity fluid. Results support continuous drug infusion over bolus dosing in the treatment for neonatal foal septicemia to optimize time that cefotaxime concentration exceeds the minimum inhibitory concentration of common equine pathogens.

  1. Assessment of use of specific features of subcutaneous insulin infusion systems and their relationship to metabolic control in patients with type 1 diabetes.

    PubMed

    Quirós, Carmen; Patrascioiu, Ioana; Giménez, Marga; Vinagre, Irene; Vidal, Mercè; Jansà, Margarita; Conget, Ignacio

    2014-01-01

    Patients with type 1 diabetes (T1DM) treated with continuous subcutaneous insulin infusion (CSII) have available several specific features of these devices. The aim of this study was to evaluate the relationship between real use of them and the degree of glycemic control in patients using this therapy. Forty-four T1DM patients on CSII therapy with or without real-time continuous glucose monitoring (CGM) were included. Data from 14 consecutive days were retrospectively collected using the therapy management software CareLink Personal/Pro(®) and HbA1c measurement performed at that period. The relationship between the frequency of usie of specific features of insulin pumps (non-sensor augmented or sensor-augmented) and glycemic control was analyzed. Mean HbA1c in the group was 7.5 ± .8%. Mean daily number of boluses administered was 5.1 ± 1.8, with 75.4% of them being bolus wizards (BW). Daily number of boluses was significantly greater in patients with HbA1c <7.5% than in those with HbA1c>7.5% (5.3 ± 1.6 vs. 4.3 ± 1.6, P=.056). There was a trend to greater use of BW in patients with better control (82.8 ± 21.4% vs. 69.9 ± 29.1%, P=.106). HbA1c was lower in patients using CGM (n=8) as compared to those not using sensor-augmented pumps (7.6 ± .8 vs 7.1 ± .7, P=.067), but the difference was not statistically significant. More frequent use of BW appears to be associated to better metabolic control in patients with T1DM using pump therapy. In standard clinical practice, augmentation of insulin pump with CGM may be associated to improved glycemic control. Copyright © 2013 SEEN. Published by Elsevier Espana. All rights reserved.

  2. The increase in fiber size in male rat gastrocnemius after chronic central leptin infusion is related to activation of insulin signaling.

    PubMed

    Burgos-Ramos, Emma; Canelles, Sandra; Rodríguez, Amaia; Frago, Laura M; Gómez-Ambrosi, Javier; Chowen, Julie A; Frühbeck, Gema; Argente, Jesús; Barrios, Vicente

    2017-09-27

    Insulin potentiates leptin effects on muscle accrual and glucose homeostasis. However, the relationship between leptin's central effects on peripheral insulin sensitivity and the associated structural changes remain unclear. We hypothesized that central leptin infusion modifies muscle size through activation of insulin signaling. Muscle insulin signaling, enzymes of fatty acid metabolism, mitochondrial respiratory chain complexes, proliferating cell nuclear antigen (PCNA) and fiber area were analyzed in the gastrocnemius of chronic central infused (L), pair-fed (PF) and control rats. PCNA-positive nuclei, fiber area, GLUT4 and glycogen levels and activation of Akt and mechanistic target of rapamycin were increased in L, with no changes in PF. Acetyl-CoA carboxylase-β mRNA levels and non-esterified fatty acid and triglyceride content were reduced and carnitine palmitoyltransferase-1b expression and mitochondrial complexes augmented in L. These results suggest that leptin promotes an increase in muscle size associated with improved insulin signaling favored by lipid profile. Copyright © 2017 Elsevier B.V. All rights reserved.

  3. A Phase 2 Study of Continuous Subcutaneous Hydrocortisone Infusion in Adults With Congenital Adrenal Hyperplasia.

    PubMed

    Nella, Aikaterini A; Mallappa, Ashwini; Perritt, Ashley F; Gounden, Verena; Kumar, Parag; Sinaii, Ninet; Daley, Lori-Ann; Ling, Alexander; Liu, Chia-Ying; Soldin, Steven J; Merke, Deborah P

    2016-12-01

    Classic congenital adrenal hyperplasia (CAH) management remains challenging, given that supraphysiologic glucocorticoid doses are often needed to optimally suppress the ACTH-driven adrenal androgen overproduction. This study sought to approximate physiologic cortisol secretion via continuous subcutaneous hydrocortisone infusion (CSHI) and evaluate the safety and efficacy of CSHI in patients with difficult-to-treat CAH. Eight adult patients with classic CAH participated in a single-center open-label phase I-II study comparing CSHI to conventional oral glucocorticoid treatment. All patients had elevated adrenal steroids and one or more comorbidities at study entry. Assessment while receiving conventional therapy at baseline and 6 months following CSHI included: 24-hour hormonal sampling, metabolic and radiologic evaluation, health-related quality-of-life (HRQoL), and fatigue questionnaires. The ability of CSHI to approximate physiologic cortisol secretion and the percent of patients with 0700-hour 17-hydroxyprogesterone (17-OHP) ≤1200 ng/dL was measured. CSHI approximated physiologic cortisol secretion. Compared with baseline, 6 months of CSHI resulted in decreased 0700-hour and 24-hour area under the curve 17-OHP, androstenedione, ACTH, and progesterone, increased osteocalcin, c-telopeptide and lean mass, and improved HRQoL (and SF-36 Vitality Score), and fatigue. One of three amenorrheic women resumed menses. One man had reduction of testicular adrenal rest tissue. CSHI is a safe and well-tolerated modality of cortisol replacement that effectively approximates physiologic cortisol secretion in patients with classic CAH poorly controlled on conventional therapy. Improved adrenal steroid control and positive effects on HRQoL suggest that CSHI should be considered a treatment option for classic CAH. The long-term effect on established comorbidities requires further study.

  4. Continuous Infusion Ketorolac for Postoperative Analgesia Following Unilateral Total Knee Arthroplasty.

    PubMed

    Schwinghammer, Amy J; Isaacs, Alex N; Benner, Rodney W; Freeman, Heather; O'Sullivan, Jacob A; Nisly, Sarah A

    2017-06-01

    Previous clinical trials have demonstrated benefit with the addition of continuous infusion (CI) ketorolac to a multimodal pain regimen in surgical patients. Data following major orthopedic surgery are minimal and conflicting. To evaluate CI ketorolac use following unilateral total knee arthroplasty (TKA) through assessment of patient-reported pain scores, opioid consumption, and safety outcomes. This was a retrospective, open-label cohort study that included patients undergoing unilateral TKA at a single-center teaching hospital. Participants were categorized into 2 study groups based on postoperative management: CI ketorolac or opioid protocol (OP). The first group received a ketorolac 30-mg bolus followed by CI 3.6 mg/h plus as-needed (PRN) opioids. The OP group received PRN narcotics in a tiered protocol. The primary end point was comparison of median pain scores. Secondary end points included opioid consumption (morphine equivalent units [MEUs]) in the first 48 hours postoperatively, length of stay, and adverse effects. Of 447 patients screened, 191 were analyzed (CI ketorolac, n = 116; OP, n = 75). Median pain scores were significantly lower in the CI ketorolac group at 48 hours postoperatively (3 [2-4] vs 3.5 [2.5-5], P = 0.033). Cumulative MEUs at 48 hours were significantly lower in the CI ketorolac group (33.9 ± 38.5 mg vs 301.6 ± 36.6 mg, P < 0.001). Patients in the CI ketorolac group experienced less respiratory depression (5.2% vs 25.3%, P < 0.001) and less naloxone administration (0% vs 8%, P = 0.002) compared with the OP group. Other adverse effects were similar among groups. Postoperative CI ketorolac improved pain control while reducing opioid consumption and adverse effects.

  5. Comparison of continuous epidural infusion and programmed intermittent epidural bolus in labor analgesia

    PubMed Central

    Lin, Yunan; Li, Qiang; Liu, Jinlu; Yang, Ruimin; Liu, Jingchen

    2016-01-01

    Background This study aims to investigate differences between continuous epidural infusion (CEI) and programmed intermittent epidural bolus (IEB) analgesia for the Chinese parturients undergoing spontaneous delivery and to approach their safety to parturients and neonates. Methods Two hundred healthy American Society of Anesthesiologists class I or II, term (≥37 weeks’ gestation), nulliparous women who requested analgesia for labor were recruited. Epidural analgesia was initiated with a solution of 0.15% ropivacaine 10 mL and maintained with 0.1% ropivacaine mixed with sufentanil 0.3 μg/mL by CEI at a rate of 5 mL/h combined with a patient-controlled epidural analgesia (PCEA) bolus of 5 mL of ropivacaine sufentanil mixture or IEB of 5 mL of ropivacaine sufentanil mixture combined with a PCEA bolus of 5 mL of ropivacaine sufentanil mixture. The lockout interval was 20 minutes in each arm between the CEI and the IEB group. After 20 minutes of first dosage, visual analog scale (VAS) score was obtained every 60 minutes. The maternal and fetal outcome and total consumption of analgesic solution were compared. Results There was no difference in demographic characteristics, duration of first and second stages, delivery methods, sensory block, fetal Apgar scores, and the maternal outcomes between the CEI and IEB groups. There was a significant difference in VAS scores and epidural ropivacaine total consumption between the two groups (IEB vs CEI: 51.27±9.61 vs 70.44±12.78 mg, P<0.01). Conclusion The use of programmed IEB mixed with PCEA improved labor analgesia compared to CEI mixed with PCEA, which could act as maintenance mode for epidural labor analgesia. PMID:27471390

  6. Continuous subcutaneous apomorphine infusion in advanced Parkinson's disease: 10-year experience with 230 patients.

    PubMed

    Sesar, Ángel; Fernández-Pajarín, Gustavo; Ares, Begoña; Rivas, María Teresa; Castro, Alfonso

    2017-05-01

    Continuous apomorphine infusion (APO) is one of the treatments available for advanced Parkinson disease (PD). Over 10 years, we have treated 230 patients with APO. Mean age was 66.8 and average evolution time at APO onset was 13.0 years. Mean duration of the treatment was 26.3 months. As of June 2016, 93 remained on the medication (active group), while 137 had stopped. This active group had mean age 67.3 at recruitment and mean evolution 14.2 years. The main indication for APO was lack of deep brain stimulation criteria (DBS). Twelve patients were on waiting list for DBS. Average time since APO onset was 40.0 months. In the active group, APO decreased off-state in 4 h and allowed reducing levodopa and dopamine agonists. Dyskinesia and balance did not worsen. Cognitive decline did not change within the first 15 months. Hallucinations were the same within the first 39 months. The presence of subcutaneous nodules was the most frequent adverse event in this group. The main reason for discontinuation was side effects, being psychosis the most common. Within the first year, 82 patients stopped APO. Eighteen of these patients eventually got DBS. APO is a good option for advanced PD, since it permits a significant reduction in off-time and other antiparkinsonian drugs. This effect is sustained over time. We have treated 132 patients for over a year. Dyskinesia seems not to worsen. Combining APO with DBS simultaneously or alternatively provides good results.

  7. Analgesic efficacy, adverse effects, and safety of oxycodone administered as continuous intravenous infusion in patients after total hip arthroplasty.

    PubMed

    Olczak, Bogumił; Kowalski, Grzegorz; Leppert, Wojciech; Zaporowska-Stachowiak, Iwona; Wieczorowska-Tobis, Katarzyna

    2017-01-01

    Total hip arthroplasty (THA) causes extensive tissue damage and severe pain. This study aimed to assess the analgesic efficacy, adverse effects (AEs), and safety of continuous intravenous (iv) oxycodone infusion with ketoprofen (injected into the iv line) in patients after THA, and to assay serum oxycodone levels. Fourteen patients, aged 59‒82 years with American Society of Anesthesiologists (ASA) classification I or III, underwent THA with intrathecal analgesia and sedation induced by iv propofol. After the surgery, oxycodone (continuous iv infusion) at a dose of 1 mg/h (five patients) or 2 mg/h (nine patients) with 100 mg ketoprofen (injected into the iv line) was administered to each patient every 12 h. Pain was assessed using a numerical rating scale (NRS: 0 - no pain, 10 - the most severe pain) at rest and during movement. AEs, including hemodynamic unsteadiness, nausea, vomiting, pruritus, cognitive impairment, and respiratory depression, were registered during the first 24 h after surgery. Oxycodone (continuous iv infusion) at a dose of 2 mg/h with ketoprofen (100 mg) administered every 12 h provided satisfactory analgesia in all nine patients without the need of rescue analgesics within the first 24 h after THA. In three out of five patients, oxycodone at 1 mg/h was effective. Oxycodone did not induce drowsiness, vomiting, pruritus, respiratory depression, or changes in blood pressure. Bradycardia appeared in two patients, and nausea was observed in one patient. Oxycodone infusion with ketoprofen administered by iv is effective in patients after THA. Intravenous infusion of oxycodone is a predictable, stable, and safe method of drug administration.

  8. Increased incidence of acute graft-versus-host disease with the continuous infusion of cyclosporine A compared to twice-daily infusion.

    PubMed

    Ogawa, N; Kanda, Y; Matsubara, M; Asano, Y; Nakagawa, M; Sakata-Yanagimoto, M; Kandabashi, K; Izutsu, K; Imai, Y; Hangaishi, A; Kurokawa, M; Tsujino, S; Ogawa, S; Aoki, K; Chiba, S; Motokura, T; Hirai, H

    2004-03-01

    We retrospectively compared the incidence of acute graft-versus-host disease (GVHD) before and after September 1999, when we changed the mode of cyclosporine A (CsA) administration from twice-daily infusions (TD) (n=58) to continuous infusion (CIF) (n=71). The incidence of grade II-IV acute GVHD in the CIF group (56%) was significantly higher than that in the TD group (27%, P=0.00022). Multivariate analysis identified only two independent significant risk factors for the development of grade II-IV acute GVHD; CIF of CsA (relative risk 2.59, 95% CI 1.46-4.60, P=0.0011) and the presence of HLA mismatch (2.01, 95% CI 1.15-3.53, P=0.014). The incidence of relapse was significantly lower in the CIF group when adjusted for disease status before transplantation (0.41, 95% CI 0.18-0.95, P=0.038), which resulted in better disease-free survival in high-risk patients (43 vs 16% at 2 years, P=0.039), but not in standard-risk patients (72 vs 80%, P=0.45). CIF of CsA with a target level of 250-400 ng/ml may not be appropriate for GVHD prophylaxis in standard-risk patients.

  9. Development and Evaluation of a Guideline for Monitoring Propylene Glycol Toxicity in Pediatric Intensive Care Unit Patients Receiving Continuous Infusion Lorazepam

    PubMed Central

    Lange, Rebecca; Gupta, Sameer

    2015-01-01

    OBJECTIVES: To develop and determine the safety of a guideline, by using osmol gap as an indicator of propylene glycol toxicity for pediatric patients receiving continuous infusion lorazepam. METHODS: From existing adult data, a guideline was developed for the use of continuous infusion lorazepam in pediatric critical care patients with recommendations for using osmol gap as an indicator of propylene glycol toxicity. A retrospective medical chart review was performed of patients receiving continuous infusion lorazepam from February 2012 to September 2012 for whom the guideline was used. RESULTS: Twenty-one patients received continuous infusion lorazepam for sedation in the pediatric intensive care unit during the 9-month study period for a total of 23 infusions. Eight patients (34.8%) had an osmol gap of ≥ 12 mOsm/kg during lorazepam infusion, and 7 patients (30.4%) did not have an elevated osmol gap at any point during the infusion. Two patients (8.6%) had clinical toxicity as indicated by elevated anion gap or lactate in addition to an osmol gap ≥ 12 mOsm/kg, while no patients experienced clinical toxicity with an osmol gap < 12 mOsm/kg. CONCLUSIONS: A guideline for the use of lorazepam infusion in pediatric critical care patients was developed and evaluated for safety. Lorazepam continuous infusions appeared to be associated with minimal toxicity in pediatric intensive care unit patients when the osmol gap monitoring guideline was used. PMID:26472950

  10. Effect of intraoperative amino acids with or without glucose infusion on body temperature, insulin, and blood glucose levels in patients undergoing laparoscopic colectomy: a preliminary report.

    PubMed

    Fujita, Yasuki; Tokunaga, Chiharu; Yamaguchi, Sayo; Nakamura, Kayo; Horiguchi, Yuu; Kaneko, Michiko; Iwakura, Takeo

    2014-09-01

    Amino acid administration helps to prevent intraoperative hypothermia but may enhance thermogenesis when combined with glucose infusion. The aim of this study was to examine the effect of intraoperative amino acid administration, with or without glucose infusion, on temperature regulation during laparoscopic colectomy. Twenty-one patients whose physical status was classified I or II by the American Society of Anesthesiologists, and who were undergoing elective laparoscopic colectomy were enrolled. The exclusion criteria were a history of diabetes and/or obesity, preoperative high levels of C-reactive protein, high blood glucose and/or body temperature after anesthesia induction, and surgical time >500 minutes. Each patient received an acetate ringer solution and was randomly assigned to one of three groups. Group A patients were given only amino acids. Group AG patients were given amino acids and glucose. Group C patients were given neither amino acids nor glucose. Tympanic membrane temperatures and blood glucose and insulin levels were measured intraoperatively. Intraoperative amino acid infusion significantly increased body temperature during surgery as compared with either Group AG or C. The blood glucose levels in Group AG were significantly higher than those in Groups A and C. However, there were no significant differences between Groups A and C. Two hours after anesthesia induction, serum insulin levels in Groups A and AG significantly increased compared with Group C. No significant differences in the postoperative complications or patient hospitalization lengths were detected between the groups. Intraoperative amino acid infusion without glucose administration maintains body temperature more effectively than combined amino acid and glucose infusion in patients undergoing laparoscopic colectomy, despite unaltered intraoperative insulin levels. Copyright © 2014. Published by Elsevier B.V.

  11. Using Insulin Infusion Sets in CSII for Longer Than the Recommended Usage Time Leads to a High Risk for Adverse Events

    PubMed Central

    Pfützner, Andreas; Sachsenheimer, Daniela; Grenningloh, Marco; Heschel, Matthias; Walther-Johannesen, Lene; Gharabli, Rabi; Klonoff, David

    2015-01-01

    Background: Infusion sets for use with insulin pumps are recommended for use for 2 to 3 days to avoid local skin reactions, for example, to the insulin formulation and preservatives like meta-cresol. However, many patients use the catheters longer for economic reasons. We performed this study to investigate the tolerability of 2-day use of infusion sets in comparison to 4-day use in a real-world setting. Methods: This prospective randomized controlled crossover study with 2 × 3-month observation periods was performed with 24 type 1 patients. At baseline, patients were trained on the use of the infusion system (Medtronic /Mio® or inset™ II) and randomized to any of the 2 treatment sequences. Observation parameters included glycemic control, frequency and nature of device-related, and procedure-related adverse events and patient preference. Results: The per-protocol analysis was performed with 22 patients (5 men, 17 women, age 39 ± 11 years, BMI 27.0 ± 3.5 kg/m2). The number of catheter related adverse events was 290 with 2-day use versus 495 with 4-day use (P < .05). The overall number of treatment related events was 750 with 2-day use versus 934 with 4-day use (P < .001). There was no difference in glycemic control between the treatment arms. Treatment satisfaction was higher with 2-day use (very high/high satisfaction: 90.4% versus 4 day-use: 77.3%, P < .05). Conclusion: Our results demonstrate that using the infusion sets for a longer usage period of 2-3 days resulted in a clinically relevant increase in treatment-related tolerability problems. Patients should be trained and encouraged not to use insulin pump infusion sets for a longer than the recommended time period. PMID:26341262

  12. A 7-day continuous infusion of PTH or PTHrP suppresses bone formation and uncouples bone turnover.

    PubMed

    Horwitz, Mara J; Tedesco, Mary Beth; Sereika, Susan M; Prebehala, Linda; Gundberg, Caren M; Hollis, Bruce W; Bisello, Alessandro; Garcia-Ocaña, Adolfo; Carneiro, Raquel M; Stewart, Andrew F

    2011-09-01

    Human in vivo models of primary hyperparathyroidism (HPT), humoral hypercalcemia of malignancy (HHM), or lactational bone mobilization for more than 48 hours have not been described previously. We therefore developed 7-day continuous-infusion models using human parathyroid hormone(1-34) [hPTH(1-34)] and human parathyroid hormone-related protein(1-36) [hPTHrP(1-36)] in healthy human adult volunteers. Study subjects developed sustained mild increases in serum calcium (10.0 mg/dL), with marked suppression of endogenous PTH(1-84). The maximal tolerated infused doses over a 7-day period (2 and 4 pmol/kg/h for PTH and PTHrP, respectively) were far lower than in prior, briefer human studies (8 to 28 pmol/kg/h). In contrast to prior reports using higher PTH and PTHrP doses, both 1,25-dihydroxyvitamin D(3) [1,25(OH)(2) D(3) ] and tubular maximum for phosphorus (TmP/GFR) remained unaltered with these low doses despite achievement of hypercalcemia and hypercalciuria. As expected, bone resorption increased rapidly and reversed promptly with cessation of the infusion. However, in contrast to events in primary HPT, bone formation was suppressed by 30% to 40% for the 7 days of the infusions. With cessation of PTH and PTHrP infusion, bone-formation markers abruptly rebounded upward, confirming that bone formation is suppressed by continuous PTH or PTHrP infusion. These studies demonstrate that continuous exposure of the human skeleton to PTH or PTHrP in vivo recruits and activates the bone-resorption program but causes sustained arrest in the osteoblast maturation program. These events would most closely mimic and model events in HHM. Although not a perfect model for lactation, the increase in resorption and the rebound increase in formation with cessation of the infusions are reminiscent of the maternal skeletal calcium mobilization and reversal that occur following lactation. The findings also highlight similarities and differences between the model and HPT. Copyright

  13. Continuous extradural infusion of ropivacaine for prevention of postoperative pain after major orthopaedic surgery.

    PubMed

    Turner, G; Blake, D; Buckland, M; Chamley, D; Dawson, P; Goodchild, C; Mezzatesta, J; Scott, D; Sultana, A; Walker, S; Hendrata, M; Mooney, P; Armstrong, M

    1996-05-01

    We studied 151 patients undergoing total hip or knee arthroplasty, or cruciate ligament reconstruction in a multicentre study in Australia and New Zealand. Patients were openly allocated randomly to one of five treatment groups or to a control group. General anaesthesia was induced after introduction of extradural block with 0.5% ropivacaine. After surgery, patients received an extradural infusion of 0.2% ropivacaine at 6, 8, 10, 12 or 14 ml h-1 or received no postoperative extradural infusion (control group). All patients had access to i.v. PCA morphine for supplementary analgesia. Morphine consumption was lower in all treatment groups compared with the control group, decreasing with increasing ropivacaine infusion rate. Median VAS scores were lower in all ropivacaine infusion groups compared with the control group for the first 10 h of the study; however by the end of the study, VAS scores were similar in all groups. The higher ropivacaine infusion rates caused a slower convergence of spread of the initial sensory block and a higher degree of motor block. The overall incidence of side effects was similar, with the exception of a higher incidence of urinary retention and hypotension in the groups receiving the higher rates of ropivacaine. The quality of treatment scores were similar for all treatment groups (Br. J. Anaesth. 1996; 76: 606-610).

  14. Continuous infusion of porcine factor VIII in patients with haemophilia A and high-responding inhibitors: stability and clinical experience.

    PubMed

    O'Gorman, P; Dimichele, D M; Kasper, C K; Mannucci, P M; Santagostini, E; Hay, C R

    2001-11-01

    A multicentre retrospective survey was conducted to assess the efficacy and side-effect profile of porcine factor VIII (pFVIII:C) given by continuous infusion (CI) to patients with congenital haemophilia A and inhibitors. Twenty-nine episodes in 18 patients were treated by CI of pFVIII:C. Efficacy was graded as good in 79% of infusions and fair in 17%. There was a failed response in only one episode. Fourteen percent of patients experienced transfusion reactions with bolus doses, but no reactions were observed in patients given CI. There were no severe reactions. All the reactions resolved following interruption of the infusion and administration of steroids. Premedication did not prevent reactions. In this series the median decrease in platelet count after bolus injection of pFVIII:C was -67 X 10(9) L(-1) compared with a median decrease of -2 x 109 L(-1) during the course of CI, thus, continuous infusion of pFVIII:C appears to have less effect on platelet count than bolus injection. An anamnestic response was associated with 77% of infusions. This high rate of anamnesis reflects patient selection, in that they were all known to have high-level high-responding FVIII inhibitors with cross-reactivity to pFVIII. After reconstitution, the pFVIII:C showed little loss in factor VIII activity in solution over a 24-h period. We conclude that pFVIII:C may be effectively administered by CI to patients with haemophilia A and high-responding FVIII inhibitors. CI is the probably the mode of administration of choice for intensive replacement therapy with pFVIII.

  15. Oxalate Nephropathy After Continuous Infusion of High-Dose Vitamin C as an Adjunct to Burn Resuscitation

    PubMed Central

    Pamplin, Jeremy; Studer, Lynette; Hughes, Rhome L.; King, Booker T.; Graybill, John C.; Chung, Kevin K.

    2016-01-01

    Fluid resuscitation is the foundation of management in burn patients and is the topic of considerable research. One adjunct in burn resuscitation is continuous, high-dose vitamin C (ascorbic acid) infusion, which may reduce fluid requirements and thus decrease the risk for over resuscitation. Research in preclinical studies and clinical trials has shown continuous infusions of high-dose vitamin C to be beneficial with decrease in resuscitative volumes and limited adverse effects. However, high-dose and low-dose vitamin C supplementation has been shown to cause secondary calcium oxalate nephropathy, worsen acute kidney injury, and delay renal recovery in non-burn patients. To the best of our knowledge, the authors present the first case series in burn patients in whom calcium oxalate nephropathy has been identified after high-dose vitamin C therapy. PMID:25812044

  16. Comparative analysis of Micrococcus luteus isolates from blood cultures of patients with pulmonary hypertension receiving epoprostenol continuous infusion.

    PubMed

    Hirata, Yoshinori; Sata, Makoto; Makiuchi, Yuko; Morikane, Keita; Wada, Akihito; Okabe, Nobuhiko; Tomoike, Hitonobu

    2009-12-01

    During the period 2002-2008, at the National Cardiovascular Center, Osaka, 28 Micrococcus luteus isolates and one Kocuria spp. isolate were obtained from blood cultures of pulmonary hypertension (PH) patients who were receiving continuous infusion therapy with epoprostenol. Pulsed-field gel electrophoresis patterns of the isolates were unrelated, suggesting that the infections had multiple origins. The preparation of epoprostenol solution by patients themselves was thought to be a risk factor.

  17. Continuous controlled-infusion of hypertonic saline solution in traumatic brain-injured patients: a 9-year retrospective study

    PubMed Central

    2011-01-01

    Introduction Description of a continuous hypertonic saline solution (HSS) infusion using a dose-adaptation of natremia in traumatic brain injured (TBI) patients with refractory intracranial hypertension (ICH). Methods We performed a single-center retrospective study in a surgical intensive care unit of a tertiary hospital. Fifty consecutive TBI patients with refractory ICH treated with continuous HSS infusion adapted to a target of natremia. In brief, a physician set a target of natremia adapted to the evolution of intracranial pressure (ICP). Flow of NaCl 20% was a priori calculated according to natriuresis, and the current and target natremia that were assessed every 4 hours. Results The HSS infusion was initiated for a duration of 7 (5 to 10) (8 ± 4) days. ICP decreased from 29 (26 to 34) (31 ± 9) mm Hg at H0 to 20 (15 to 26) (21 ± 8) mm Hg at H1 (P < 0.05). Cerebral perfusion pressure increased from 61 (50 to 70) (61 ± 13) mm Hg at H0 up to 67 (60 to 79) (69 ± 12) mm Hg at H1 (P < 0.05). No rebound of ICH was reported after stopping continuous HSS infusion. Natremia increased from 140 (138 to 143) (140 ± 4) at H0 up to 144 (141 to 148) (144 ± 4) mmol/L at H4 (P < 0.05). Plasma osmolarity increased from 275 (268 to 281) (279 ± 17) mmol/L at H0 up to 290 (284 to 307) (297 ± 17) mmol/L at H24 (P < 0.05). The main side effect observed was an increase in chloremia from 111 (107 to 119) (113 ± 8) mmol/L at H0 up to 121 (117 to 124) (121 ± 6) mmol/L at H24 (P < 0.05). Neither acute kidney injury nor pontine myelinolysis was recorded. Conclusions Continuous HSS infusion adapted to close biologic monitoring enables long-lasting control of natremia in TBI patients along with a decreased ICP without any rebound on infusion discontinuation. PMID:22035596

  18. A continuous infusion of a minor histocompatibility antigen-immunodominant peptide induces a delay of male skin graft rejection.

    PubMed

    Sireci, Guido; Barera, Annalisa; Macaluso, Pasquale; Di Sano, Caterina; Bonanno, Cesira T; Pio La Manna, Marco; Di Liberto, Diana; Dieli, Francesco; Salerno, Alfredo

    2009-01-01

    We previously reported that an inhibition of antigen-specific Interferon-gamma release and cytotoxicity occurs after a continuous infusion of an HY immunodominant peptide although this treatment is not able to cause a significant delay of male skin grafts rejection. In vivo administration of high doses of an HY peptide, through mini-osmotic pumps, in naïve female mice was used to study the effects on the male skin grafts rejection. A continuous infusion of 1mg of an HY peptide induces a significant delay of male skin graft rejection. In vitro HY-specific Interferon-gamma release was inhibited adding peptide-specific suppressor cells: the ability to inhibit Interferon-gamma release was evident when two HY peptides were present on the same dendritic cells indicating that the suppressor cells exert "linked-suppression". The phenotype of the suppressor cells is CD8(+)CD28(-) and these cells express more CD62 ligand and FOXP3 than controls. Suppressor cells were able to cause a significant delay of rejection of male skin grafts when injected in naive female mice. The inhibitory effects of these suppressor cells seem to be due to the impairment of antigen presentation; down-regulation of B7 molecules on dendritic cells occurred. Taken all together, our data demonstrate that a continuous infusion of an immunodominant HY peptide induces a T CD8 suppressor subset able to inhibit immune responses to male tissues and cells.

  19. Effect of programmed intermittent epidural boluses and continuous epidural infusion on labor analgesia and obstetric outcomes: a randomized controlled trial.

    PubMed

    Ferrer, Leopoldo E; Romero, David J; Vásquez, Oscar I; Matute, Ednna C; Van de Velde, Marc

    2017-09-07

    Continuous epidural infusion and programmed intermittent epidural boluses are analgesic techniques routinely used for pain relief in laboring women. We aimed to assess both techniques and compare them with respect to labor analgesia and obstetric outcomes. After Institutional Review Board approval, 132 laboring women aged between 18 and 45 years were randomized to epidural analgesia of 10 mL of a mixture of 0.1% bupivacaine plus 2 µg/mL of fentanyl either by programmed intermittent boluses or continuous infusion (66 per group). Primary outcome was quality of analgesia. Secondary outcomes were duration of labor, total drug dose used, maternal satisfaction, sensory level, motor block level, presence of unilateral motor block, hemodynamics, side effects, mode of delivery, and newborn outcome. Patients in the programmed intermittent epidural boluses group received statistically less drug dose than those with continuous epidural infusion (24.9 vs 34.4 mL bupivacaine; P = 0.01). There was no difference between groups regarding pain control, characteristics of block, hemodynamics, side effects, and Apgar scores. Our study evidenced a lower anesthetic consumption in the programmed intermittent boluses group with similar labor analgesic control, and obstetric and newborn outcomes in both groups.

  20. DNA alkylation and tumor induction in regenerating rat liver after cell cycle-related continuous N-nitrosodimethylamine infusion

    SciTech Connect

    Rabes, H.M.; Kerler, R.; Wilhelm, R.

    1983-01-01

    Synchronized regenerating rat liver after partial hepatectomy was used to study cell cycle-related DNA base alkylation and liver carcinogenesis. A continuous iv infusion of (/sup 14/C)N-nitrosodimethylamine (DMN) at a dose of 0.5 mg/kg/hour was given to inbred male Wistar Af/Han rats over a period of 8 hours either during the G1 phase, hydroxyurea-synchronized DNA synthesis, or the G2+M-phase of regenerating liver or to untreated rats (G0-phase liver--carcinogen dose, 1.5 mg/kg/hour). Two hours after the end of the infusion, the amount of 7-methylguanine was highest in the G0-phase liver, with a decrease in the G1 phase, the S-phase, and the G2+M-phase. After continuous DMN exposure, the O6-methylguanine:7-methylguanine ratio was lower in the S-phase and G2+M-phase livers than in the G0-phase and G1-phase livers, indicating an increased O6-methylguanine repair during DNA synthesis and the G2+M-phase. Liver tumors in rats treated by continuous DMN infusion either during the G0 phase or the S-phase developed only after carcinogen exposure during DNA synthesis.

  1. Continuous subcutaneous hydrocortisone infusion therapy in Addison's disease: a randomized, placebo-controlled clinical trial.

    PubMed

    Gagliardi, Lucia; Nenke, Marni A; Thynne, Tilenka R J; von der Borch, Jenny; Rankin, Wayne A; Henley, David E; Sorbello, Jane; Inder, Warrick J; Torpy, David J

    2014-11-01

    Patients with Addison's disease (AD) report impaired subjective health status (SHS). Since cortisol exhibits a robust circadian cycle that entrains other biological clocks, impaired SHS may be due to the noncircadian cortisol profile achieved with conventional glucocorticoid replacement. Continuous subcutaneous hydrocortisone infusion (CSHI) reproduces a circadian cortisol profile, but its effects on SHS have not been objectively evaluated. The aim of this study was to determine the effect of CSHI on SHS in AD. This was a multicentre, double-blind, placebo-controlled trial of CSHI vs oral glucocorticoid therapy. Participants received in random order 4 weeks of: CSHI and oral placebo, and subcutaneous placebo and oral hydrocortisone, separated by a 2-week washout period. SHS was assessed using the Short-Form 36 (SF-36), General Health Questionnaire (GHQ-28), Fatigue Scale (FS), Gastrointestinal Symptom Rating Scale (GSRS); and Addison's Quality of Life Questionnaire (AddiQoL). Participants were asked their (blinded) treatment preference. Twenty-four hour urine free cortisol (UFC) and diurnal salivary cortisol collections compared cortisol exposure during each treatment. Ten participants completed the study. Baseline SHS scores (mean ± SE) were consistent with mild impairment: SF-36 physical component summary 48.4 (± 2.4), mental component summary 53.3 (± 3.0); GHQ-28 18.1 (± 3.3); GSRS 3.7 (± 1.6), and AddiQoL 94.7 (± 3.7). FS was similar to other AD cohorts 13.5 (± 1.0) (P = 0.82). UFC between treatments was not different (P = 0.87). The salivary cortisol at 0800 h was higher during CSHI (P = 0.03), but not at any other time points measured. There was no difference between the treatments in the SHS assessments. Five participants preferred CSHI, four oral hydrocortisone, and one was uncertain. Biochemical measurements indicate similar cortisol exposure during each treatment period, although a more circadian pattern was evident during CSHI. CSHI does not

  2. Comparison of daily glucose excursion by continuous glucose monitoring between type 2 diabetic patients receiving preprandial insulin aspart or postprandial insulin glulisine.

    PubMed

    Ohta, Akio; Arai, Kaori; Nishine, Ami; Sada, Yoshiyuki; Kato, Hiroyuki; Fukuda, Hisashi; Asai, Shiko; Nagai, Yoshio; Katabami, Takuyuki; Tanaka, Yasushi

    2013-01-01

    Insulin glulisine (Glu) is a rapidly-acting insulin analog with a faster onset of action than the other insulin analogs of its class, which are insulin aspart (Asp) and insulin lispro (Lisp). While insulin Glu is usually injected just before meals, postprandial injection may help to avoid unexpected postprandial hypoglycemia or hyperglycemia by adjusting the insulin dosage according to food intake. However, the effect of postprandial insulin Glu on the glucose profile has not been evaluated. The aim of this study was to compare daily glucose excursion by continuous glucose monitoring (CGM) between multiple daily doses of preprandial insulin Asp or postprandial insulin Glu. In a randomized cross-over trial, we performed CGM to evaluate the 48-hour glucose profile during treatment with the same dosage of insulin Asp just before each meal in 12 hospitalized patients with type 2 diabetes. Patients also received the same dosage of long-acting insulin glargine at bedtime. The average glucose level, standard deviation of the glucose level, mean amplitude of glucose excursion, and daily glucose profile did not differ between preprandial Asp and postprandial Glu. The incidence of hypoglycemic episodes (glucose level<70 mg/dL with or without symptoms) and the area under the curve of glucose<70 mg/dL also did not differ between the two insulin regimens. Multiple daily injections of preprandial Asp and postprandial Glu achieved the same daily glucose excursion profile. Postprandial injection of Glu may provide greater flexibility for patients who require insulin therapy.

  3. Should we continue or stop insulin sensitizing drugs during pregnancy?

    PubMed

    Norman, Robert J; Wang, Jim X; Hague, William

    2004-06-01

    The use of insulin sensitizing drugs such as metformin in polycystic ovary syndrome has been increasingly popular and validated by systematic reviews. There has also been an interest in the use of metformin for gestational diabetes. However, administration of metformin to prevent miscarriage is controversial and widespread use of this drug in early pregnancy requires investigation. There are claims that miscarriage and gestational diabetes are more common in polycystic ovary syndrome and that use of insulin sensitizers improves outcomes dramatically. This review suggests there is no evidence for increased risk of miscarriage solely due to polycystic ovary syndrome and that there are insufficient data for promoting therapy with metformin. There is some reason for use of metformin in mid-pregnancy for gestational diabetes but better evidence from randomized controlled trials is urgently needed. The use of metformin in early pregnancy for reducing the risk of miscarriage should be avoided outside of the context of properly designed prospective randomized trials. Safety in early pregnancy appears to be reassuring but not completely proven. The use of metformin in mid-pregnancy for gestational diabetes appears more logical but also needs adequate trials before general use is advocated.

  4. Efficacy of Continuous S(+)-Ketamine Infusion for Postoperative Pain Control: A Randomized Placebo-Controlled Trial.

    PubMed

    Miziara, Luiz Eduardo de Paula Gomes; Simoni, Ricardo Francisco; Esteves, Luís Otávio; Cangiani, Luis Henrique; Grillo-Filho, Gil Fernando Ribeiro; Paula, Anderson Garcia Lima E

    2016-01-01

    Aim. A double-blind, randomized, placebo-controlled trial was designed to evaluate the efficacy of continuous intraoperative infusion of S(+)-ketamine under intravenous anesthesia with target-controlled infusion of remifentanil and propofol for postoperative pain control. Methods. Forty-eight patients undergoing laparoscopic cholecystectomy were assigned to receive continuous S(+)-ketamine infusion at a rate of 0.3 mg·kg(-1)·h(-1) (n = 24, intervention group) or an equivalent volume of saline at the same rate (n = 24, placebo group). The same target-controlled intravenous anesthesia was induced in both groups. Pain was assessed using a 0 to 10 verbal numeric rating scale during the first 12 postoperative hours. Pain scores and morphine consumption were recorded in the postanesthesia care unit (PACU) and at 4 and 12 hours after surgery. Results. Pain scores were lower in the intervention group at all time points. Morphine consumption did not differ significantly between groups during PACU stay, but it was significantly lower in the intervention group at each time point after PACU discharge (P = 0.0061). At 12 hours after surgery, cumulative morphine consumption was also lower in the intervention group (5.200 ± 2.707) than in the placebo group (7.525 ± 1.872). Conclusions. Continuous S(+)-ketamine infusion during laparoscopic cholecystectomy under target-controlled intravenous anesthesia provided better postoperative pain control than placebo, reducing morphine requirement. Trial Registration. This trial is registered with ClinicalTrials.gov NCT02421913.

  5. Decreased incidence of acute graft-versus-host disease by continuous infusion of cyclosporine with a higher target blood level.

    PubMed

    Oshima, Kumi; Kanda, Yoshinobu; Nakasone, Hideki; Arai, Shunya; Nishimoto, Nahoko; Sato, Hiroyuki; Watanabe, Takuro; Hosoya, Noriko; Izutsu, Koji; Asai, Takashi; Hangaishi, Akira; Motokura, Toru; Chiba, Shigeru; Kurokawa, Mineo

    2008-03-01

    Cyclosporine A (CsA) is the mainstay of pharmacologic prevention of acute graft-versus-host disease (GVHD). We previously reported that continuous infusion of CsA with a target blood level between 250 and 400 ng/ml significantly increased the incidence of acute GVHD compared to twice-daily infusion with a target trough level between 150 and 300 ng/ml. Thus, we raised the target level of CsA continuous infusion to 450-550 ng/ml. We treated 33 patients with the higher target level (CsA500) and compared the efficacy and toxicity with those in the 33 historical control patients (CsA300 group). Other transplantation procedures were not changed. The patients' characteristics were equivalent. The average CsA concentration was adjusted around 500 ng/ml and the actual daily dose was maintained at the initial dose (CsA 3mg/kg/day). Toxicities were equivalently observed among the two groups. The incidence of grades II-IV acute GVHD was significantly lower in the CsA500 group (27 vs. 52%, P = 0.033). The target level of CsA was identified as an independent significant risk factor for grades II-IV acute GVHD (P = 0.039), adjusted for the presence of HLA mismatch. The incidence of chronic GVHD was also decreased in the CsA500 group (47 vs. 73%, P = 0.016). We conclude that the toxicity of the continuous CsA infusion with a target level of 450-550 ng/ml is acceptable and the efficacy to prevent acute GVHD is significant. A larger comparative study is warranted to confirm these findings.

  6. A Feasibility Study of Bihormonal Closed-Loop Blood Glucose Control Using Dual Subcutaneous Infusion of Insulin and Glucagon in Ambulatory Diabetic Swine

    PubMed Central

    El-Khatib, Firas H.; Jiang, John; Damiano, Edward R.

    2009-01-01

    Background We sought to test the feasibility and efficacy of bihormonal closed-loop blood glucose (BG) control that utilizes subcutaneous (SC) infusion of insulin and glucagon, a model-predictive control algorithm for determining insulin dosing, and a proportional-derivative control algorithm for determining glucagon dosing. Methods Thirteen closed-loop experiments (∼7–27 h in length) were conducted in six ambulatory diabetic pigs weighing 26–50 kg. In all experiments, venous BG was sampled through a central line in the vena cava. Efficacy was evaluated in terms of the controller's ability to regulate BG in response to large meal disturbances (∼5 g of carbohydrate per kilogram of body mass per meal) based only on regular frequent venous BG sampling and requiring only the subject's weight for initialization. Results Closed-loop results demonstrated successful BG regulation to normoglycemic range, with average insulin-to-carbohydrate ratios between ∼1:20 and 1:40 U/g. The total insulin bolus doses averaged ∼6 U for a meal containing ∼6 g per kilogram body mass. Mean BG values in two 24 h experiments were ∼142 and ∼155 mg/dl, with the total daily dose (TDD) of insulin being ∼0.8–1.0 U per kilogram of body mass and the TDD of glucagon being ∼0.02–0.05 mg. Results also affirmed the efficacy of SC doses of glucagon in staving off episodic hypoglycemia. Conclusions We demonstrate the feasibility of bihormonal closed-loop BG regulation using a control system that employs SC infusion of insulin and glucagon as governed by an algorithm that reacts only to BG without any feed-forward information regarding carbohydrate consumption or physical activity. As such, this study can reasonably be regarded as the first practical implementation of an artificial endocrine pancreas that has a hormonally derived counterregulatory capability. PMID:20144330

  7. The effectiveness of continuous subcutaneous insulin pumps with continuous glucose monitoring in outpatient adolescents with type 1 diabetes: A systematic review.

    PubMed

    Matsuda, Erin; Brennan, Patricia

    2012-01-01

    The review question is: Are metabolic outcomes improved in outpatient adolescents (aged 13 to 19 years) with type 1 diabetes on a Continuous Subcutaneous Insulin Infusion (CSII) when continuous glucose monitoring is used, compared to self-glucose monitoring alone? Type 1 diabetes is the most common childhood paediatric disease, characterised by impairment of insulin producing βeta-cells in the pancreas. Internationally, there is variation in the incidence of type 1 diabetes in paediatric patients. According to the Center for Disease Control and Prevention (CDC) and the SEARCH for Diabetes in Youth Study Group, the overall incidence rate of this autoimmune disease is 24.3/100,000 in those 19 years of age . Annually, more than 15,000 children and adolescents are diagnosed in the United States (US) . From 1990 to 1999, the World Health Organization (WHO) launched the Multinational Project for Childhood Diabetes (DIAMOND), which was tasked with assessing type 1 diabetes in those 14 years or younger worldwide . Finland was discovered to have the highest age-adjusted incidence at 40.9 cases per 100,000/year. The lowest age-adjusted incidence is in China and Venezuela at 0.1 cases per 100,000/year. Globally, the largest increase in incidence is in those aged 10 to 14 years . This systematic review will focus on adolescent patients with type 1 diabetes, aged 13 to 19 years who manage their diabetes with an insulin pump.Patients with type 1 diabetes mellitus typically present with a history of polydipsia, polyuria, polyphagia, and weight loss . Initial findings include hyperglycemia, glycosuria, and ketones in the blood or urine . In 2009, the International Expert Committee deemed a haemoglobin A1C (glycosylated haemoglobin) of 6.5% or higher to be the standard for diagnosis . The American Diabetes Association (ADA) as well as the International Diabetes Federation and the European Association Study of Diabetes (EASD) accept this measure as the diagnostic tool for diabetes

  8. Impact of renal replacement modalities on the clearance of piperacillin-tazobactam administered via continuous infusion in critically ill patients.

    PubMed

    Roger, Claire; Cotta, Menino O; Muller, Laurent; Wallis, Steven C; Lipman, Jeffrey; Lefrant, Jean-Yves; Roberts, Jason A

    2017-08-01

    This prospective pharmacokinetic study aimed to compare the clearance of piperacillin-tazobactam administered as a 24-h continuous infusion between continuous venovenous haemodiafiltration (CVVHDF) and continuous venovenous haemofiltration (CVVH) applied at equal dose in critically ill patients. A loading dose of 4.5 g of piperacillin-tazobactam followed by a continuous infusion (500 mg/h) was administered to patients randomized to receive CVVHDF or CVVH. Serial pre- and postfilter blood samples were drawn during an 8-h sampling interval. Piperacillin plasma concentrations were measured using a validated chromatography method. Piperacillin pharmacokinetics were calculated using a non-compartmental approach. In total, 212 piperacillin plasma concentrations were determined. Median [interquartile range (IQR)] total piperacillin clearance was 7.5 (5.9-11.2) L/h in the CVVHDF group and 4.7 (4.5-9.6) L/h in the CVVH group (P = 0.21). Median (IQR) piperacillin clearance related to continuous renal replacement therapy (CRRT) was 3.0 (2.7-3.2) L/h in the CVVHDF group and 2.6 (1.9-3.0) L/h in the CVVH group (P = 0.29). Mean (standard deviation) steady state concentrations were 68.4 (25.8) mg/L in the CVVHDF group and 89.1 (35.6) mg/L in the CVVH group (P = 0.16). The estimated unbound concentrations resulting from piperacillin continuous infusion were above the target susceptibility breakpoint (16 mg/L) for the entire dosing interval (100% fT>MIC) in all study patients. In the present study, higher (but not significantly) piperacillin clearance and lower piperacillin exposure were observed in patients receiving CVVHDF compared with CVVH. In patients receiving CRRT, the use of piperacillin continuous infusion should be considered to ensure optimal exposure for less susceptible pathogens. Copyright © 2017. Published by Elsevier B.V.

  9. Should β-lactam antibiotics be administered by continuous infusion in critically ill patients? A survey of Australia and New Zealand intensive care unit doctors and pharmacists.

    PubMed

    Cotta, Menino O; Dulhunty, Joel M; Roberts, Jason A; Myburgh, John; Lipman, Jeffrey

    2016-06-01

    Although there is a biological precedent for administration of β-lactam antibiotics by continuous or extended infusion, there is no definitive evidence of a survival benefit compared with intermittent administration. The aim of this study was to explore clinician uncertainty with regard to the administration of β-lactam antibiotics by continuous infusion. Doctors and pharmacists in Australian and New Zealand intensive care units (ICUs) were surveyed to investigate current β-lactam antibiotic administration practices as well as the degree of uncertainty regarding the benefit of continuous infusion of two commonly used broad-spectrum β-lactams, namely meropenem and piperacillin/tazobactam (TZP). There were 111 respondents to the survey. Intermittent infusion was reported as standard practice for meropenem (73.9%) and TZP (82.0%). A greater proportion of pharmacists compared with doctors believed continuous infusion to be more effective than intermittent administration (85.4% vs. 34.3%, respectively; P <0.001). Both groups reported uncertainty as to whether administration by continuous infusion resulted in better patient outcomes (65.9% and 74.6%, respectively; P = 0.85). Overall, 91.0% of respondents were prepared to enrol eligible patients into a definitive randomised controlled trial on β-lactam antibiotic administration. In conclusion, there is equipoise among clinicians working in Australian and New Zealand ICUs as to whether administration by continuous infusion offers a survival benefit in critically ill patients.

  10. Continuous infusion of tracer norepinephrine may miscalculate unidirectional nerve uptake of norepinephrine in humans

    SciTech Connect

    Henriksen, J.H.; Christensen, N.J.; Ring-Larsen, H. )

    1989-08-01

    In order to evaluate uptake kinetics of norepinephrine (NE) in different tissues, a catheterization study was performed in control subjects (n = 6) and patients with enhanced sympathetic nervous activity (cirrhosis, n = 12) during constant intravenous infusion of L(3H)norepinephrine ((3H)NE) for 75 minutes. In spite of a higher NE spillover from kidneys in patients compared with controls (82 vs. 49 ng/min, p less than 0.01), renal extraction ratios of (3H)NE were similar in the two groups (0.33 vs. 0.32, NS), and no significant change was observed during the time of infusion. In contrast, liver-intestine extraction ratios of (3H)NE decreased significantly and equally with infusion time in patients (from 0.57 to 0.44, p less than 0.01) and controls (from 0.59 to 0.46, p less than 0.01). This was observed despite the fact that spillover of NE from this vascular bed was observed only in patients with cirrhosis and not in controls (41 vs. -5 ng/min, p less than 0.02). In the lower limb, net release of NE was similar in patients and controls, and extraction ratios of (3H)NE decreased almost equally with infusion time (from 0.35 to 0.30, p less than 0.01 and from 0.40 to 0.24, p less than 0.1, respectively). Whole-body clearance of (3H)NE decreased over time in patients (-6%, p less than 0.01) and controls (-20%, p less than 0.01), but significant difference was not observed between the groups. We conclude that failure to attain a steady state with respect to (3H)NE removal was demonstrated in areas of large tissue volume relative to blood flow.

  11. Continuous Cefazolin Infusion To Treat Bone and Joint Infections: Clinical Efficacy, Feasibility, Safety, and Serum and Bone Concentrations▿

    PubMed Central

    Zeller, Valérie; Durand, Frédérick; Kitzis, Marie-Dominique; Lhotellier, Luc; Ziza, Jean-Marc; Mamoudy, Patrick; Desplaces, Nicole

    2009-01-01

    Cefazolin has been used for many years to treat bone and joint infections. Because of its time-dependent antimicrobial activity, continuous infusion would potentially be beneficial. We report on the feasibility, safety, and efficacy of prolonged continuous intravenous cefazolin therapy in a cohort of 100 patients, their serum cefazolin levels, and the concomitant bone cefazolin concentrations in 8 of them. This retrospective cohort study included all the patients treated for bone or joint infection with a continuous cefazolin infusion administered over a 12-h period twice daily for ≥2 weeks. Drug monitoring was performed at least twice for all the patients. Serum and bone cefazolin concentrations were determined by standardized disk diffusion microbiological assays. The absence of clinical, biological, and radiological signs of infection after 2 years of follow-up and the same criteria after 1 year of follow-up defined cures and probable cures, respectively. The median treatment duration was 42 days, and the median daily cefazolin dose was 6 g. Half of the patients received parenteral antibiotic therapy on an outpatient basis. Two moderate-grade adverse events were observed. The median serum cefazolin concentrations were 63 μg/ml (range, 13 to 203 μg/ml) and 57 μg/ml (range, 29 to 128 μg/ml) on days 2 to 10 and days 11 to 21, respectively. The median bone cefazolin concentration reached 13.5 μg/g (range, 3.5 to 29 μg/g). The median bone concentration/serum concentration ratio was 0.25 (range, 0.06 to 0.41). Among 88 patients with a median follow-up of 25 months (range, 12 to 53 months), 52 were considered cured and 29 were considered probably cured. Thus, the treatment of bone and joint infections with a prolonged continuous intravenous cefazolin infusion was feasible, effective, well-tolerated, safe, and convenient, making it a strong candidate for home therapy. PMID:19075069

  12. Lack of difference between continuous versus intermittent heparin infusion on maintenance of intra-arterial catheter in postoperative pediatric surgery: a randomized controlled study

    PubMed Central

    Witkowski, Maria Carolina; de Moraes, Maria Antonieta P.; Firpo, Cora Maria F.

    2013-01-01

    OBJECTIVE: To compare two systems of arterial catheters maintenance in postoperative pediatric surgery using intermittent or continuous infusion of heparin solution and to analyze adverse events related to the site of catheter insertion and the volume of infused heparin solution. METHODS: Randomized control trial with 140 patients selected for continuous infusion group (CIG) and intermittent infusion group (IIG). The variables analyzed were: type of heart disease, permanence time and size of the catheter, insertion site, technique used, volume of heparin solution and adverse events. The descriptive variables were analyzed by Student's t-test and the categorical variables, by chi-square test, being significant p<0.05. RESULTS: The median age was 11 (0-22) months, and 77 (55%) were females. No significant differences between studied variables were found, except for the volume used in CIG (12.0±1.2mL/24 hours) when compared to IIG (5.3±3.5mL/24 hours) with p<0.0003. CONCLUSIONS: The continuous infusion system and the intermittent infusion of heparin solution can be used for intra-arterial catheters maintenance in postoperative pediatric surgery, regardless of patient's clinical and demographic characteristics. Adverse events up to the third postoperative day occurred similarly in both groups. However, the intermittent infusion system usage in underweight children should be considered, due to the lower volume of infused heparin solution [ClinicalTrials.gov Identifier: NCT01097031]. PMID:24473958

  13. Postoperative Pain Control with the Fentanyl Patch and Continuous Paravertebral Anesthetic Infusion after Posterior Occipitocervical Junction Surgery.

    PubMed

    Sivakumar, Walavan; Karsy, Michael; Brock, Andrea; Schmidt, Richard H

    2016-06-17

    Postoperative pain is a significant concern for patients who undergo surgery via a midline posterior approach to the occipitocervical junction and spinal axis. The development of the disposable, ambulatory pain pump presents a novel alternative for treatment of postoperative pain. The authors describe a multimodal treatment algorithm for postoperative pain after posterior occipitocervical junction surgery that uses the On-Q pain catheter system (I-Flow Corp., Lake Forest, CA) and a fentanyl patch. The On-Q PainBuster catheter system is a disposable, ambulatory device that allows for continuous anesthetic delivery directly into or adjacent to the wound. On-Q catheters are placed in the nuchal musculature for continuous infusion of 0.5% bupivacaine. The On-Q catheter infusion is continued for three days, and the catheters are then withdrawn. Patients are also provided with a transdermal fentanyl patch at the start of surgery. In regards to complications at our facility, there have been no cases of respiratory depression or arrest postoperatively and no wound infections, but one case of inadvertent subdural placement. The technique described for the use of the fentanyl patch and a continuous anesthetic delivery device in surgery of the occipitocervical junction presents a novel alternative to the current standard of care in pain control after suboccipital decompression.

  14. Postoperative Pain Control with the Fentanyl Patch and Continuous Paravertebral Anesthetic Infusion after Posterior Occipitocervical Junction Surgery

    PubMed Central

    Sivakumar, Walavan; Karsy, Michael; Brock, Andrea

    2016-01-01

    Postoperative pain is a significant concern for patients who undergo surgery via a midline posterior approach to the occipitocervical junction and spinal axis. The development of the disposable, ambulatory pain pump presents a novel alternative for treatment of postoperative pain. The authors describe a multimodal treatment algorithm for postoperative pain after posterior occipitocervical junction surgery that uses the On-Q pain catheter system (I-Flow Corp., Lake Forest, CA) and a fentanyl patch. The On-Q PainBuster catheter system is a disposable, ambulatory device that allows for continuous anesthetic delivery directly into or adjacent to the wound. On-Q catheters are placed in the nuchal musculature for continuous infusion of 0.5% bupivacaine. The On-Q catheter infusion is continued for three days, and the catheters are then withdrawn. Patients are also provided with a transdermal fentanyl patch at the start of surgery. In regards to complications at our facility, there have been no cases of respiratory depression or arrest postoperatively and no wound infections, but one case of inadvertent subdural placement. The technique described for the use of the fentanyl patch and a continuous anesthetic delivery device in surgery of the occipitocervical junction presents a novel alternative to the current standard of care in pain control after suboccipital decompression. PMID:27433423

  15. Renal and segmental pancreatic grafting with draining of exocrine secretion and initial continuous intravenous cyclosporin A in a patient with insulin-dependent diabetes and renal failure

    PubMed Central

    Calne, R Y; White, D J G; Rolles, K; Duffy, T J; Kass, T

    1982-01-01

    A patient with renal failure and insulin-dependent diabetes received renal and segmental pancreatic allografts from the same donor, with exocrine drainage of the pancreas being directed into the bowel. An attempt was made to maintain the serum concentrations of cyclosporin A between 300 and 1000 μg/l to avoid serious nephrotoxicity and rejection. Considerable difficulty was experienced in controlling the serum concentrations even with continuous intravenous infusion. When the concentrations were maintained between 300 and 1000 μg/l function in both allografts was satisfactory. At seven months the patient required no insulin and had good renal function. He was not receiving corticosteroids. ImagesFIG 1 PMID:6809184

  16. Impact of the Type of Continuous Insulin Administration on Metabolism in a Diabetic Rat Model

    PubMed Central

    Schaschkow, A.; Dal, S.; Langlois, A.; Seyfritz, E.; Sookhareea, C.; Bietiger, W.; Peronet, C.; Jeandidier, N.; Pinget, M.; Sigrist, S.

    2016-01-01

    Exogenous insulin is the only treatment available for type 1 diabetic patients and is mostly administered by subcutaneous (SC) injection in a basal and bolus scheme using insulin pens (injection) or pumps (preimplanted SC catheter). Some divergence exists between these two modes of administration, since pumps provide better glycaemic control compared to injections in humans. The aim of this study was to compare the impacts of two modes of insulin administration (single injections of long-acting insulin or pump delivery of rapid-acting insulin) at the same dosage (4 IU/200 g/day) on rat metabolism and tissues. The rat weight and blood glucose levels were measured periodically after treatment. Immunostaining for signs of oxidative stress and for macrophages was performed on the liver and omental tissues. The continuous insulin delivery by pumps restored normoglycaemia, which induced the reduction of both reactive oxygen species and macrophage infiltration into the liver and omentum. Injections controlled the glucose levels for only a short period of time and therefore tissue stress and inflammation were elevated. In conclusion, the insulin administration mode has a crucial impact on rat metabolic parameters, which has to be taken into account when studies are designed. PMID:27504460

  17. Insulin

    MedlinePlus

    ... Information by Audience For Women Women's Health Topics Insulin Share Tweet Linkedin Pin it More sharing options ... medicines. You can do it. Back to Top Insulin Safety Tips Never drink insulin. Do not share ...

  18. High-dose, continuous-infusion cyclophosphamide, cytarabine, vincristine, and prednisone for remission induction in refractory adult acute leukemia.

    PubMed

    Guthrie, T H

    1987-04-01

    Fifteen consecutive patients with refractory adult acute leukemia (RAAL) were treated with a combination of high-dose, continuous-infusion cyclophosphamide, cytarabine, vincristine, and prednisone (Hi-COAP). The initial nine patients received cyclophosphamide 350 mg/m2 as a 24-hour intravenous (IV) infusion over 5 days; cytarabine, 100 mg/m2 IV bolus every 12 hours for ten doses; vincristine, 2.0 mg IV bolus on day 1; and prednisone, 100 mg orally for 7 days. The last six patients had the cyclophosphamide infusion lengthened to 7 days, and the cytarabine increased to 14 doses. All patients were evaluable for toxicity and response. Seven patients (47%) obtained a complete remission and six patients (40%) a partial remission. Median duration of all remissions has been 7.0 months with a range of 1 to 32 months. Toxicity has been limited to primarily myelosuppression with no hemorrhagic cystitis, central nervous system (CNS), hepatic, or pulmonary toxicity noted. Gastrointestinal toxicity was mild, with no effect on nutritional status noted. Median duration of complete responders was 8.5 months. Thus, Hi-COAP demonstrates promising efficacy with minimal toxicity in RAAL and warrants further exploration in multiinstitutional trials.

  19. A prospective evaluation of propylene glycol clearance and accumulation during continuous-infusion lorazepam in critically ill patients.

    PubMed

    Nelsen, Jamie L; Haas, Curtis E; Habtemariam, Bahru; Kaufman, David C; Partridge, Amy; Welle, Stephen; Forrest, Alan

    2008-01-01

    Propylene glycol is a commonly used diluent in several pharmaceutical preparations, including the sedative lorazepam. Fifty critically ill patients receiving continuous-infusion lorazepam for a minimum of 36 hours were prospectively evaluated to determine the extent of propylene glycol accumulation over time, characterize propylene glycol clearance in the presence of critical illness, and develop a pharmacokinetic model that would predict clearance based on patient-specific clinical, laboratory, and demographic factors. In this cohort, the median lorazepam infusion rate was 2.1 mg/h (0.5-18). Propylene glycol concentration correlated poorly with osmolality, osmol gap, and lactate. In all, 8 patients (16%) had significant propylene glycol accumulation (>25mg/dL). When propylene glycol concentrations were >25 mg/dL, the median lorazepam infusion rate before sample collection was higher, 6.4 (1.9-11.3) versus 2.0 (0.5-7.4) mg/h (P =.0003). A linear first-order model with interoccasion variability on clearance adjusted for total body weight and Acute Physiology and Chronic Health Evaluation II score predicted propylene glycol concentration.

  20. Enhancing the [13C]bicarbonate signal in cardiac hyperpolarized [1-13C]pyruvate MRS studies by infusion of glucose, insulin and potassium.

    PubMed

    Lauritzen, Mette Hauge; Laustsen, Christoffer; Butt, Sadia Asghar; Magnusson, Peter; Søgaard, Lise Vejby; Ardenkjær-Larsen, Jan Henrik; Åkeson, Per

    2013-11-01

    A change in myocardial metabolism is a known effect of several diseases. MRS with hyperpolarized (13)C-labelled pyruvate is a technique capable of detecting changes in myocardial pyruvate metabolism, and has proven to be useful for the evaluation of myocardial ischaemia in vivo. However, during fasting, the myocardial glucose oxidation is low and the fatty acid oxidation (β-oxidation) is high, which complicates the interpretation of pyruvate metabolism with the technique. The aim of this study was to investigate whether the infusion of glucose, insulin and potassium (GIK) could increase the myocardial glucose oxidation in the citric acid cycle, reflected as an increase in the [(13)C]bicarbonate signal in cardiac hyperpolarized [1-(13)C]pyruvate MRS measurements in fasted rats. Two groups of rats were infused with two different doses of GIK and investigated by MRS after injection of hyperpolarized [1-(13)C]pyruvate. No [(13)C]bicarbonate signal could be detected in the fasted state. However, a significant increase in the [(13)C]bicarbonate signal was observed by the infusion of a high dose of GIK. This study demonstrates that a high [(13)C]bicarbonate signal can be achieved by GIK infusion in fasted rats. The increased [(13)C]bicarbonate signal indicates an increased flux of pyruvate through the pyruvate dehydrogenase enzyme complex and an increase in myocardial glucose oxidation through the citric acid cycle.

  1. Therapeutic drug monitoring of continuous-infusion acylovir for disseminated herpes simplex virus infection in a neonate receiving concurrent extracorporeal life support and continuous renal replacement therapy.

    PubMed

    Cies, Jeffrey J; Moore, Wayne S; Miller, Kyle; Small, Christine; Carella, Dominick; Conley, Susan; Parker, Jason; Shea, Paul; Chopra, Arun

    2015-02-01

    Disseminated herpes simplex virus (HSV) infection in neonates represents a devastating entity that yields high mortality. Acyclovir is the primary antiviral agent used to treat life-threatening HSV infections in neonates; however, even though the agent has reduced morbidity overall from these infections, mortality with disseminated disease remains high. Currently, to our knowledge, no data exist regarding therapeutic drug monitoring of acyclovir in the setting of extracorporeal life support (ECLS) or continuous renal replacement therapy (CRRT) coupled with ECLS. We describe the case of a 14-day-old female with disseminated HSV-1 infection that progressed to fulminant hepatic and renal failure, necessitating the use of ECLS for hemodynamic support and CRRT as a treatment modality for hepatic and renal failure. The standard dosage of acyclovir 20 mg/kg/dose intravenously every 8 hours had been initiated, but after conversion to ECLS and CRRT, the patient's dosage was increased to 30 mg/kg/dose every 8 hours. After a repeat viral load remained unchanged from the initial viral load at 1 × 10(8)  copies/ml, the patient was transitioned from intermittent dosing to a continuous infusion of acyclovir added to the dialysate solution for CRRT at a concentration of 5.5 mg/L. To provide an optimal outcome, dosing was designed to maintain acyclovir plasma concentrations of at least 3 mg/L in order to maintain an acyclovir concentration of at least 1 mg/L in the cerebrospinal fluid. The patient's acyclovir serum concentrations measured at 24 and 72 hours after starting continuous-infusion acyclovir via the dialysate were 8.8 and 5.3 mg/L, respectively, allowing for a continuous serum concentration above 3 mg/L. Unfortunately, before a repeat viral load could be obtained to assess the efficacy of the continuous infusion acyclovir, the patient experienced an intracerebral hemorrhage as a complication related to ECLS after which technological support was withdrawn

  2. In Vivo MR Imaging of Pulmonary Perfusion and Gas Exchange in Rats via Continuous Extracorporeal Infusion of Hyperpolarized 129Xe

    PubMed Central

    Cleveland, Zackary I.; Möller, Harald E.; Hedlund, Laurence W.; Nouls, John C.; Freeman, Matthew S.; Qi, Yi; Driehuys, Bastiaan

    2012-01-01

    Background Hyperpolarized (HP) 129Xe magnetic resonance imaging (MRI) permits high resolution, regional visualization of pulmonary ventilation. Additionally, its reasonably high solubility (>10%) and large chemical shift range (>200 ppm) in tissues allow HP 129Xe to serve as a regional probe of pulmonary perfusion and gas transport, when introduced directly into the vasculature. In earlier work, vascular delivery was accomplished in rats by first dissolving HP 129Xe in a biologically compatible carrier solution, injecting the solution into the vasculature, and then detecting HP 129Xe as it emerged into the alveolar airspaces. Although easily implemented, this approach was constrained by the tolerable injection volume and the duration of the HP 129Xe signal. Methods and Principal Findings Here, we overcome the volume and temporal constraints imposed by injection, by using hydrophobic, microporous, gas-exchange membranes to directly and continuously infuse 129Xe into the arterial blood of live rats with an extracorporeal (EC) circuit. The resulting gas-phase 129Xe signal is sufficient to generate diffusive gas exchange- and pulmonary perfusion-dependent, 3D MR images with a nominal resolution of 2×2×2 mm3. We also show that the 129Xe signal dynamics during EC infusion are well described by an analytical model that incorporates both mass transport into the blood and longitudinal relaxation. Conclusions Extracorporeal infusion of HP 129Xe enables rapid, 3D MR imaging of rat lungs and, when combined with ventilation imaging, will permit spatially resolved studies of the ventilation-perfusion ratio in small animals. Moreover, EC infusion should allow 129Xe to be delivered elsewhere in the body and make possible functional and molecular imaging approaches that are currently not feasible using inhaled HP 129Xe. PMID:22363613

  3. Effects of a bolus injection of 5-fluorouracil on dihydropyrimidine dehydrogenase activity in rats receiving continuous infusion of 5-fluorouracil.

    PubMed

    Kobuchi, Shinji; Hayashi, Asuka; Taniguchi, Mayu; Ito, Yukako; Tamura, Takao; Sakaeda, Toshiyuki

    2016-09-01

    The options for improving the chemotherapeutic regimen consisting of bolus plus infusion of 5-fluorouracil (5-FU) include omitting the 5-FU bolus injection. We examined the effects of a 5-FU bolus injection on the activity of dihydropyrimidine dehydrogenase (DPD), which is the first and rate-limiting enzyme of 5-FU catabolism, in rats. The rats were divided into three groups, and then continuous infusion (50 mg/m(2)/h) for 4 h was started with a bolus injection of saline, 20 mg/kg 5-FU, or 60 mg/kg 5-FU. Plasma 5-FU, uracil (Ura), dihydrouracil (UH2) levels, and hepatic DPD activity were determined after administration of 5-FU. The half-life after the end of the infusion (t 1/2, 4-8 h) of 5-FU in the rats given the bolus injection was significantly longer than in those that had been given saline, and it increased with increasing 5-FU bolus injection dosage (r = 0.801, p < 0.01). The plasma UH2/Ura ratio, an indirect biomarker of hepatic DPD activity, tended to be lower in the rats that had received a 5-FU bolus injection than in those that had not, and it remained low after infusion ended. The hepatic DPD activity in rats that had received a 5-FU bolus injection was significantly lower than in those that had not. Negative correlation was observed between DPD activity and bolus injection dosage (r = -0.691, p < 0.05). A bolus injection suppresses hepatic DPD activity and its effects are dependent on dosage, resulting in slower elimination of 5-FU from the blood and contributing to long-term systemic exposure to 5-FU.

  4. Combination of continuous intravenous infusion using a mixture of guaifenesin-ketamine-medetomidine and sevoflurane anesthesia in horses.

    PubMed

    Yamashita, K; Satoh, M; Umikawa, A; Tsuda, A; Yajima, Y; Tsubakishita, S; Seno, T; Katoh, S; Izumisawa, Y; Kotani, T

    2000-03-01

    The anesthetic and cardiovascular effects of a combination of continuous intravenous infusion using a mixture of 100 g/L guaifenesin-4 g/L ketamine-5 mg/L medetomidine (0.25 ml/kg/hr) and oxygen-sevoflurane (OS) anesthesia (GKM-OS anesthesia) in horses were evaluated. The right carotid artery of each of 12 horses was raised surgically into a subcutaneous position under GKM-OS anesthesia (n=6) or OS anesthesia (n=6). The end-tidal concentration of sevoflurane (EtSEV) required to maintain surgical anesthesia was around 1.5% in GKM-OS and 3.0% in OS anesthesia. Mean arterial blood pressure (MABP) was maintained at around 80 mmHg under GKM-OS anesthesia, while infusion of dobutamine (0.39+/-0.10 microg/kg/min) was necessary to maintain MABP at 60 mmHg under OS anesthesia. The horses were able to stand at 36+/-26 min after cessation of GKM-OS anesthesia and at 48+/-19 minutes after OS anesthesia. The cardiovascular effects were evaluated in 12 horses anesthetized with GKM-OS anesthesia using 1.5% of EtSEV (n=6) or OS anesthesia using 3.0% of EtSEV (n=6). During GKM-OS anesthesia, cardiac output and peripheral vascular resistance was maintained at about 70% of the baseline value before anesthesia, and MABP was maintained over 70 mmHg. During OS anesthesia, infusion of dobutamine (0.59+/-0.24 microg/kg/min) was necessary to maintain MABP at 70 mmHg. Infusion of dobutamine enabled to maintaine cardiac output at about 80% of the baseline value; however, it induced the development of severe tachycardia in a horse anesthetized with sevoflurane. GKM-OS anesthesia may be useful for prolonged equine surgery because of its minimal cardiovascular effect and good recovery.

  5. Continuous infraclavicular perineural infusion with clonidine and ropivacaine compared with ropivacaine alone: a randomized, double-blinded, controlled study.

    PubMed

    Ilfeld, Brian M; Morey, Timothy E; Enneking, F Kayser

    2003-09-01

    Although clonidine has been shown to increase the duration of local anesthetic action and prolong postoperative analgesia when included in single-injection nerve blocks, a controlled investigation of the efficacy of this practice to improve analgesia for continuous perineural local anesthetic infusion has not been reported. In this study, ambulatory patients (n = 34) undergoing moderately painful upper extremity orthopedic surgery received an infraclavicular brachial plexus block (mepivacaine 1.5%, epinephrine 2.5 micro g/mL, and bicarbonate 0.1 mEq/mL) and a perineural catheter before surgery. After surgery, patients were discharged home with a portable infusion pump delivering either ropivacaine 0.2% or ropivacaine 0.2% plus clonidine 1 micro g/mL via the catheter for 3 days (basal, 8 mL/h; patient-controlled bolus, 2 mL every 20 min). Investigators and patients were blinded to random group assignment. Daily end-points included pain scores, patient-controlled bolus doses, oral analgesic use, sleep quality, and symptoms of catheter- or infusion-related complications. Adding clonidine to ropivacaine resulted in a statistically significant decrease in the number of self-administered 2-mL bolus doses on postoperative Days 0 and 1 (P < 0.02), but this decreased actual local anesthetic consumption by an average of only 2-7 mL/d (P < 0.02). There were no statistically significant differences between the two groups for any of the other variables investigated, including sleep quality or oral analgesic requirements. We conclude that adding 1 micro g/mL of clonidine to a ropivacaine infraclavicular perineural infusion does not provide clinically relevant improvements in analgesia, sleep quality, or oral analgesic requirements for ambulatory patients having moderately painful upper extremity surgery.

  6. Successful treatment of pulmonary blastomycosis with continuously infused amphotericin B deoxycholate after failure with liposomal amphotericin B.

    PubMed

    Ariano, Robert E; Mitchelmore, Bradley R; Lagacé-Wiens, Philippe Rs; Zelenitsky, Sheryl A

    2013-06-01

    To describe a case of successful treatment of severe pulmonary blastomycosis with amphotericin B deoxycholate after failure of liposomal amphotericin B. A 35-year-old male was exposed to damp decomposing wood while cleaning his basement. He subsequently developed a cough, malaise, fever, nausea, vomiting, and diarrhea. He was admitted to the hospital and intubated for worsening pulmonary symptoms. Microscopic examination of his sputum indicated Blastomyces dermatitidis. Liposomal amphotericin B was administered for 6 days, but the patient's temperature reached 39.6 °C and his white blood cell (WBC) count reached 52,300/μL. Extensive consolidation of both lungs fields was observed on chest X-ray. Because of progressive clinical deterioration, the treatment was switched to amphotericin B deoxycholate by continuous infusion. That change resulted in clinical improvement, with abrupt reductions (within 48 hours) in temperature and the WBC count. By day 14 of therapy (day 8 of amphotericin B deoxycholate), the chest X-ray showed improvement in diffuse airspace filling. After 16 days of amphotericin B treatment, intravenous followed by oral voriconazole was administered for 3 months. Eight months later the patient's strength had improved significantly, but he still had occasional episodes of shortness of breath. The management of blastomycosis is challenging because of the lack of clinically supporting data. The gold standard for severe pulmonary blastomycosis had been amphotericin B deoxycholate; however, improved safety data with liposomal amphotericin B for other fungal infections has suggested this as an effective alternative. This report describes a patient with severe pulmonary blastomycosis failing 6 days of liposomal amphotericin B, yet he tolerated and clinically responded to continuous infusion of amphotericin B deoxycholate. Based on this case report and a simulated pharmacokinetic/pharmaco dynamic analysis, continuous infusion of amphotericin B deoxycholate

  7. Insulin therapy in children and adolescents.

    PubMed

    Tamborlane, William V; Sikes, Kristin A

    2012-03-01

    Insulin therapy is the mainstay of treatment in children and adolescents with type 1 diabetes (T1D) and is a key component in the treatment of type 2 diabetes (T2D) in this population as well. A major aim of current insulin replacement therapy is to simulate the normal pattern of insulin secretion as closely as possible. This aim can best be achieved with basal-bolus therapy using multiple daily injections (MDI) or continuous insulin infusion (CSII) pump therapy. Only a few years ago, options for insulin formulations were limited. There are now more than 10 varieties of biosynthetic human and analogue insulin.

  8. Regulation of insulin-stimulated glucose uptake in rat white adipose tissue upon chronic central leptin infusion: effects on adiposity.

    PubMed

    Bonzón-Kulichenko, Elena; Fernández-Agulló, Teresa; Moltó, Eduardo; Serrano, Rosario; Fernández, Alejandro; Ros, Manuel; Carrascosa, José M; Arribas, Carmen; Martínez, Carmen; Andrés, Antonio; Gallardo, Nilda

    2011-04-01

    Leptin enhances the glucose utilization in most insulin target tissues and paradoxically decreases it in white adipose tissue (WAT), but knowledge of the mechanisms underlying the inhibitory effect of central leptin on the insulin-dependent glucose uptake in WAT is limited. After 7 d intracerebroventricular leptin treatment (0.2 μg/d) of rats, the overall insulin sensitivity and the responsiveness of WAT after acute in vivo insulin administration were analyzed. We also performed unilateral WAT denervation to clarify the role of the autonomic nervous system in leptin effects on the insulin-stimulated [(3)H]-2-deoxyglucose transport in WAT. Central leptin improved the overall insulin sensitivity but decreased the in vivo insulin action in WAT, including insulin receptor autophosphorylation, insulin receptor substrate-1 tyrosine-phosphorylation, and Akt activation. In this tissue, insulin receptor substrate-1 and glucose transporter 4 mRNA and protein levels were down-regulated after central leptin treatment. Additionally, a remarkable up-regulation of resistin, together with an augmented expression of suppressor of cytokine signaling 3 in WAT, was also observed in leptin-treated rats. As a result, the insulin-stimulated glucose transporter 4 insertion at the plasma membrane and the glucose uptake in WAT were impaired in leptin-treated rats. Finally, denervation of WAT abolished the inhibitory effect of central leptin on glucose transport and decreased suppressor of cytokine signaling 3 and resistin levels in this tissue, suggesting that resistin, in an autocrine/paracrine manner, might be a mediator of central leptin antagonism of insulin action in WAT. We conclude that central leptin, inhibiting the insulin-stimulated glucose uptake in WAT, may regulate glucose availability for triacylglyceride formation and accumulation in this tissue, thereby contributing to the control of adiposity.

  9. A prospective, randomized, blinded-endpoint, controlled study - continuous epidural infusion versus programmed intermittent epidural bolus in labor analgesia.

    PubMed

    Nunes, Joana; Nunes, Sara; Veiga, Mariano; Cortez, Mara; Seifert, Isabel

    2016-01-01

    There is evidence that administration of a programmed intermittent epidural bolus (PIEB) compared to continuous epidural infusion (CEI) leads to greater analgesia efficacy and maternal satisfaction with decreased anesthetic interventions. In this study, 166 women with viable pregnancies were included. After an epidural loading dose of 10mL with Ropivacaine 0.16% plus Sufentanil 10μg, parturient were randomly assigned to one of three regimens: A - Ropivacaine 0.15% plus Sufentanil 0.2μg/mL solution as continuous epidural infusion (5mL/h, beginning immediately after the initial bolus); B - Ropivacaine 0.1% plus Sufentanil 0.2μg/mL as programmed intermittent epidural bolus and C - Same solution as group A as programmed intermittent epidural bolus. PIEB regimens were programmed as 10mL/h starting 60min after the initial bolus. Rescue boluses of 5mL of the same solution were administered, with the infusion pump. We evaluated maternal satisfaction using a verbal numeric scale from 0 to 10. We also evaluated adverse, maternal and neonatal outcomes. We analyzed 130 pregnants (A=60; B=33; C=37). The median verbal numeric scale for maternal satisfaction was 8.8 in group A; 8.6 in group B and 8.6 in group C (p=0.83). We found a higher caesarean delivery rate in group A (56.7%; p=0.02). No differences in motor block, instrumental delivery rate and neonatal outcomes were observed. Maintenance of epidural analgesia with programmed intermittent epidural bolus is associated with a reduced incidence of caesarean delivery with equally high maternal satisfaction and no adverse outcomes. Copyright © 2015 Sociedade Brasileira de Anestesiologia. Published by Elsevier Editora Ltda. All rights reserved.

  10. [A prospective, randomized, blinded-endpoint, controlled study - continuous epidural infusion versus programmed intermittent epidural bolus in labor analgesia].

    PubMed

    Nunes, Joana; Nunes, Sara; Veiga, Mariano; Cortez, Mara; Seifert, Isabel

    2016-01-01

    There is evidence that administration of a programmed intermittent epidural bolus (PIEB) compared to continuous epidural infusion (CEI) leads to greater analgesia efficacy and maternal satisfaction with decreased anesthetic interventions. In this study, 166 women with viable pregnancies were included. After an epidural loading dose of 10mL with Ropivacaine 0.16% plus Sufentanil 10μg, parturient were randomly assigned to one of three regimens: A - Ropivacaine 0.15% plus Sufentanil 0.2μg/mL solution as continuous epidural infusion (5mL/h, beginning immediately after the initial bolus); B - Ropivacaine 0.1% plus Sufentanil 0.2μg/mL as programmed intermittent epidural bolus and C - Same solution as group A as programmed intermittent epidural bolus. PIEB regimens were programmed as 10mL/h starting 60min after the initial bolus. Rescue boluses of 5mL of the same solution were administered, with the infusion pump. We evaluated maternal satisfaction using a verbal numeric scale from 0 to 10. We also evaluated adverse, maternal and neonatal outcomes. We analyzed 130 pregnants (A=60; B=33; C=37). The median verbal numeric scale for maternal satisfaction was 8.8 in group A; 8.6 in group B and 8.6 in group C (p=0.83). We found a higher caesarean delivery rate in group A (56.7%; p=0.02). No differences in motor block, instrumental delivery rate and neonatal outcomes were observed. Maintenance of epidural analgesia with programmed intermittent epidural bolus is associated with a reduced incidence of caesarean delivery with equally high maternal satisfaction and no adverse outcomes. Copyright © 2015 Sociedade Brasileira de Anestesiologia. Publicado por Elsevier Editora Ltda. All rights reserved.

  11. Pharmacokinetics of an extended 4-hour infusion of piperacillin-tazobactam in critically ill patients undergoing continuous renal replacement therapy.

    PubMed

    Awissi, Don-Kelena; Beauchamp, Annie; Hébert, Elisabeth; Lavigne, Viviane; Munoz, Danya Lucia; Lebrun, Geneviève; Savoie, Michel; Fagnan, Mylène; Amyot, Julie; Tétreault, Nicolas; Robitaille, Robert; Varin, France; Lavallée, Christian; Pichette, Vincent; Leblanc, Martine

    2015-06-01

    To evaluate the pharmacokinetic and pharmacodynamic profiles of piperacillin-tazobactam administered as a 4-hour infusion in critically ill patients undergoing continuous renal replacement therapy (CRRT). Prospective, observational, pharmacokinetic study. Intensive care unit of a tertiary care hospital in Montréal, Canada. Twenty critically ill adults who were undergoing continuous venovenous hemodiafiltration and receiving a 4-hour infusion of piperacillin 4 g-tazobactam 0.5 g every 8 hours for a documented or suspected infection. Blood samples were collected every hour over an 8-hour dosing interval. Prefilter and postfilter blood samples, and effluent and urine samples were also collected. The primary outcome was the proportion of patients who achieved an unbound piperacillin plasma concentration above a target minimum inhibitory concentration (MIC) of 64 mg/L (MIC that inhibits 90% of isolates for Pseudomonas aeruginosa) for at least 50% of the dosing interval; 18 (90%) of the 20 patients achieved this outcome. In all patients, the free piperacillin concentrations were above the Pseudomonas aeruginosa breakpoint of 16 mg/L for the entire time interval. Regarding piperacillin pharmacokinetic parameters, the median (interquartile range) minimum unbound plasma concentration was 65.15 mg/L (51.30-89.30), maximum unbound plasma concentration was 141.3 mg/L (116.75-173.90), sieving coefficient was 0.809 (0.738-0.938), total clearance was 65.82 ml/minute (53.79-102.87), and renal clearance was 0.16 ml/minute (0.05-3.04). The median CRRT dose was 32.0 ml/kg/h (25.0-39.8). Administration of a 4-hour infusion of piperacillin-tazobactam was associated with a favorable pharmacodynamic profile in patients undergoing CRRT. Concentrations associated with maximal activity were attained in our patients. © 2015 Pharmacotherapy Publications, Inc.

  12. Serum concentrations of cefotaxime and its metabolite desacetyl-cefotaxime in infants and children during continuous infusion.

    PubMed

    Bertels, R A; Semmekrot, B A; Gerrits, G P; Mouton, J W

    2008-10-01

    Continuous infusion of cefotaxime, as opposed to intermittent infusion, seems to be advantageous for a number of reasons. However, few data exist on pharmacokinetics of cefotaxime and its metabolite in infants and children. As part of a quality assessment program, concentrations of cefotaxime and its metabolite desacetyl-cefotaxime were examined. Infants and children (age 0-17 years) routinely received cefotaxime by continuous intravenous infusion and had blood samples taken on days 1, 3, and 5 after start of therapy. Measurements were performed by high-performance liquid chromatography (HPLC) of cefotaxime and desacetyl-cefotaxime. Patients receiving a dosage of 100 mg/kg/day had a mean cefotaxime concentration of 24.9 mg/l on day 1, ranging from 0.6 to 182.6 mg/l (N = 222). Cefotaxime concentrations in infants younger than 1 week of age showed the largest variation and significantly decreased on consecutive days (p < 0.001, N = 17), together with a significant drop in the cefotaxime-desacetyl-cefotaxime (cef-des) ratio (p = 0.003, N = 16). Cefotaxime clearance increased significantly during the first days after birth (p = 0.024, N = 16). Patients older than 1 week showed negative and significant correlations of cefotaxime concentrations with calculated glomerular filtration rates (p < 0.0001, N = 73), with no significant change in the cef- des ratio on consecutive days. Overall, cefotaxime concentrations varied widely between patients, in particular in those younger than 1 week. Our data suggest that liver metabolism as well as renal excretion contribute to total body clearance of cefotaxime and increase during the first few days of live.

  13. GBR12909 attenuates amphetamine-induced striatal dopamine release as measured by [(11)C]raclopride continuous infusion PET scans.

    PubMed

    Villemagne, V L; Wong, D F; Yokoi, F; Stephane, M; Rice, K C; Matecka, D; Clough, D J; Dannals, R F; Rothman, R B

    1999-09-15

    Major neurochemical effects of methamphetamine include release of dopamine (DA), serotonin (5-HT), and norepinephrine (NE) via a carrier-mediated exchange mechanism. Preclinical research supports the hypothesis that elevations of mesolimbic DA mediate the addictive and reinforcing effects of methamphetamine and amphetamine. This hypothesis has not been adequately tested in humans. Previous in vivo rodent microdialysis demonstrated that the high affinity DA uptake inhibitor, GBR12909, attenuates cocaine- and amphetamine-induced increases in mesolimbic DA. The present study determined the ability of GBR12909 to attenuate amphetamine-induced increases in striatal DA as measured by [(11)C]raclopride continuous infusion positron emission tomography (PET) scans in two Papio anubis baboons. [(11)C]Raclopride was given in a continuous infusion paradigm resulting in a flat volume of distribution vs. time for up to 45 min postinjection. At that time, a 1.5 mg/kg amphetamine i.v. bolus was administered which caused a significant (30.3%) reduction in the volume of distribution (V(3)"). The percent reduction in the volume of distribution and, hence, a measure of the intrasynaptic DA release ranged between 22-41%. GBR12909 (1 mg/kg, slow i.v. infusion) was administered 90 min before the administration of the radiotracer. The comparison of the volume of distribution before and after administration of GBR12909 showed that GBR12909 inhibited amphetamine-induced DA release by 74%. These experiments suggest that GBR12909 is an important prototypical medication to test the hypothesis that stimulant-induced euphoria is mediated by DA and, if the DA hypothesis is correct, a potential treatment agent for cocaine and methamphetamine abuse. Furthermore, this quantitative approach demonstrates a way of testing various treatment medications, including other forms of GBR12909 such as a decanoate derivative.

  14. Insulin pump-associated adverse events are common, but not associated with glycemic control, socio-economic status, or pump/infusion set type.

    PubMed

    Ross, P; Gray, A R; Milburn, J; Kumarasamy, I M; Wu, F; Farrand, S; Armishaw, J; Wiltshire, E; Rayns, J; Tomlinson, P; Wheeler, B J

    2016-12-01

    While there have been many outcome-focussed studies examining insulin pump therapy, only a few have looked at potential adverse events (AEs), with none examining the relationship between AEs and pump/infusion set type, ethnicity or socio-economic status. In addition, current data on the incidence and characteristics of pump-associated AEs are confined to one paediatric centre. We aimed to describe the incidence, characteristics and potential predictors of insulin pump-associated AEs in New Zealand adults and children with T1DM. We approached adults and families of children with T1DM on insulin pumps in four main New Zealand centres. Participants completed a questionnaire examining pump-related issues they had experienced in the preceding 12 months. Response rate was 64 % with 174 of 270 eligible people participating in the study. 84 % of subjects reported one or more AEs, with an overall AE incidence of 3.42 per person/year (95 % CI 3.14, 3.73). An event serious enough to require a hospital presentation occurred in 9.8 %, all but one reporting high ketones or diabetic ketoacidosis (DKA). Set/site problems were the AE most commonly reported (by 53 % of respondents), followed by cutaneous complications (43 %) and pump malfunction (38 %). Few predictors of AEs (of any type) were found; however, a negative binomial regression model found that a longer duration of pumping (p = 0.018) and age <18 years (p = 0.043) were both associated with fewer AEs (all types combined). Insulin pump-associated AEs are very common. However, few variables are predictive of them with no relationships seen with glycaemic control, socio-economic status, pump manufacturer or infusion set type. Based on these findings, AEs should be anticipated in both adults and children, with anticipatory patient education and training recommended for their successful and safe use.

  15. Regional myocardial lidocaine concentration following continuous intravenous infusion early and later after myocardial infarction

    SciTech Connect

    Zito, R.A.; Caride, V.J.; Holford, T.; Zaret, B.L.

    1982-09-01

    The regional concentration of lidocaine using a double constant infusion technique (250 micrograms/kg/min x 15 minutes followed by 35 micrograms/kg/mg/min x 120 minutes) was studied immediately (2 hours) in seven dogs and 24 hours (six dogs) after myocardial infarction. Tissue levels were determined by gas chromatography and related to regional myocardial blood flow as determined by the radioactive microsphere technique in multiple samples. At 2 hours after infarction a significantly higher lidocaine concentration (4.1 +/- 0.42 micrograms/g) was found in zones with greatly reduced blood flow (regional myocardial blood flow less than 0.2 ml/min per g) when compared with that (2.6 +/- 0.19 micrograms/g) in zones with normal blood flow (regional myocardial blood flow greater than 0.8 ml/min per g) (p less than 0.01). In contrast, in the 24 hour model the opposite situation was observed. Although the concentration of lidocaine in the infarct zone was substantial, a significant decline in lidocaine tissue concentration was found in the zones of lowest blood flow (regional myocardial blood flow less than 0.2 ml/min per g) when compared with that in normal zones (1.76 +/- 0.21 versus 3.38 +/- 0.21 micrograms/g, p less than 0.001). In addition, no significant differences in lidocaine concentrations were found between endocardium and epicardium in any of the groups other than those related to regional myocardial blood flow. Thus, with the double constant infusion technique, lidocaine reached normal and ischemic myocardium in concentrations equivalent to therapeutic plasma concentrations, even in lower infarct blood flow zones, with no significant differences between endocardium and epicardium. Of perhaps greater significance, the age of the ischemic insult is an important determinant of lidocaine tissue distribution in infarcted myocardium.

  16. The pharmacokinetics of cytarabine in dogs when administered via subcutaneous and continuous intravenous infusion routes.

    PubMed

    Crook, K I; Early, P J; Messenger, K M; Muñana, K R; Gallagher, R; Papich, M G

    2013-08-01

    This crossover study compared the pharmacokinetics of cytarabine in six healthy dogs following intravenous constant rate infusion (CRI) and subcutaneous (SC) administrations, as these are two routes of administration commonly employed in the treatment of meningoencephalitis of unknown etiology. Each dog received a SC cytarabine injection of 50 mg/m(2) or an 8 h CRI of 25 mg/m(2) per hour, with a 7-day washout before receiving the alternative treatment. Blood samples were collected for 16 h after CRI initiation and for 8 h after SC injection. Plasma concentrations were measured by high-pressure liquid chromatography (HPLC). Pharmacokinetic parameters were estimated using the best-fit compartmental analysis for both CRI and SC routes. Terminal half-life (T(1/2) ) of cytarabine was 1.35 ± 0.3 and 1.15 ± 0.13 h after SC administration and CRI, respectively. Mean peak concentration (Cmax ) was 2.88 and 2.80 μg/mL for SC and CRI administration, respectively. Volume of distribution was 0.66 ± 0.07 l/kg. The 8-h CRI produced steady-state plasma concentrations as determined by consecutive measurement that did not decline until the end of the infusion. The SC administration did not achieve steady-state concentrations because cytarabine administered by this route was rapidly absorbed and eliminated quickly. The steady state achieved with the cytarabine CRI may produce a more prolonged exposure of cytarabine at cytotoxic levels in plasma compared to the concentrations after SC administration.

  17. Acute diuretic effect of continuous intravenous infusion of an aqueous extract of Coriandrum sativum L. in anesthetized rats.

    PubMed

    Aissaoui, Abderahim; El-Hilaly, Jaouad; Israili, Zafar H; Lyoussi, Badiâa

    2008-01-04

    The present investigation was carried out to evaluate the acute diuretic activity of continuous intravenous infusion of an aqueous extract of the seed of Coriandrum sativum L. Apiaceae (coriander) in rats. The aqueous extract of coriander seed was administered by continuous intravenous infusion (120 min) at two doses (40 and 100mg/kg) to anesthetized Wistar rats. Furosemide (10mg/kg), a standard diuretic was used as the reference drug. Excretion of water and electrolytes (sodium, potassium and chloride) in urine was measured, and glomerular filtration rate (equal to creatinine clearance) was determined. The crude aqueous extract of coriander seeds increased diuresis, excretion of electrolytes, and glomerular filtration rate in a dose-dependent way; furosemide was more potent as a diuretic and saluretic. The mechanism of action of the plant extract appears to be similar to that of furosemide. The aqueous extract of coriander seed possesses diuretic and saluretic activity, thus, validating the use of coriander as a diuretic plant in Moroccan pharmacopoeia.

  18. Continuous Regional Arterial Infusion of Protease Inhibitors Has No Efficacy in the Treatment of Severe Acute Pancreatitis

    PubMed Central

    Horibe, Masayasu; Sasaki, Mitsuhito; Sanui, Masamitsu; Sugiyama, Daisuke; Iwasaki, Eisuke; Yamagishi, Yoshiyuki; Sawano, Hirotaka; Goto, Takashi; Ikeura, Tsukasa; Hamada, Tsuyoshi; Oda, Takuya; Yasuda, Hideto; Shinomiya, Wataru; Miyazaki, Dai; Hirose, Kaoru; Kitamura, Katsuya; Chiba, Nobutaka; Ozaki, Tetsu; Yamashita, Takahiro; Koinuma, Toshitaka; Oshima, Taku; Yamamoto, Tomonori; Hirota, Morihisa; Moriya, Takashi; Shirai, Kunihiro; Mayumi, Toshihiko; Kanai, Takanori

    2017-01-01

    Objective The aim of this study is to assess the effectiveness of continuous regional arterial infusion (CRAI) of protease inhibitors in patients with severe acute pancreatitis (SAP) including acute necrotizing pancreatitis. Methods This retrospective study was conducted among 44 institutions in Japan from 2009 to 2013. Patients 18 years or older diagnosed with SAP according to the criteria of the Japanese Ministry of Health, Labour and Welfare study group (2008) were consecutively enrolled. We evaluated the association between CRAI of protease inhibitors and mortality, incidence of infection, and the need for surgical intervention using multivariable logistic regression analysis. Results Of 1159 patients admitted, 1097 patients with all required data were included for analysis. Three hundred and seventy-four (34.1%) patients underwent CRAI of protease inhibitors and 723 (65.9%) did not. In multivariable analysis, CRAI of protease inhibitors was not associated with a reduction in mortality, infection rate, or need for surgical intervention (odds ratio [OR] 0.79, 95% confidence interval [CI] 0.47–1.32, P = 0.36; OR 0.97, 95% CI 0.61–1.54, P = 0.89; OR 0.76, 95% CI 0.50–1.15, P = 0.19; respectively). Conclusions Continuous regional arterial infusion of protease inhibitors was not efficacious in the treatment of patients with SAP. PMID:27977624

  19. Continuous versus short-term infusion of cefuroxime: assessment of concept based on plasma, subcutaneous tissue, and bone pharmacokinetics in an animal model.

    PubMed

    Tøttrup, Mikkel; Bibby, Bo M; Hardlei, Tore F; Bue, Mats; Kerrn-Jespersen, Sigrid; Fuursted, Kurt; Søballe, Kjeld; Birke-Sørensen, Hanne

    2015-01-01

    The relatively short half-lives of most β-lactams suggest that continuous infusion of these time-dependent antimicrobials may be favorable compared to short-term infusion. Nevertheless, only limited solid-tissue pharmacokinetic data are available to support this theory. In this study, we randomly assigned 12 pigs to receive cefuroxime as either a short-term or continuous infusion. Measurements of cefuroxime were obtained every 30 min in plasma, subcutaneous tissue, and bone. For the measurements in solid tissues, microdialysis was applied. A two-compartment population model was fitted separately to the drug concentration data for the different tissues using a nonlinear mixed-effects regression model. Estimates of the pharmacokinetic parameters and time with concentrations above the MIC were derived using Monte Carlo simulations. Except for subcutaneous tissue in the short-term infusion group, the tissue penetration was incomplete for all tissues. For short-term infusion, the tissue penetration ratios were 0.97 (95% confidence interval [CI], 0.67 to 1.39), 0.61 (95% CI, 0.51 to 0.73), and 0.45 (95% CI, 0.36 to 0.56) for subcutaneous tissue, cancellous bone, and cortical bone, respectively. For continuous infusion, they were 0.53 (95% CI, 0.33 to 0.84), 0.38 (95% CI, 0.23 to 0.57), and 0.27 (95% CI, 0.13 to 0.48) for the same tissues, respectively. The absolute areas under the concentration-time curve were also lower in the continuous infusion group. Nevertheless, a significantly longer time with concentrations above the MIC was found for continuous infusion up until MICs of 4, 2, 2, and 0.5 μg/ml for plasma and the same three tissues mentioned above, respectively. For drugs with a short half-life, like cefuroxime, continuous infusion seems to be favorable compared to short-term infusion; however, incomplete tissue penetration and high MIC strains may jeopardize the continuous infusion approach. Copyright © 2015, American Society for Microbiology. All Rights

  20. Continuous versus Short-Term Infusion of Cefuroxime: Assessment of Concept Based on Plasma, Subcutaneous Tissue, and Bone Pharmacokinetics in an Animal Model

    PubMed Central

    Bibby, Bo M.; Hardlei, Tore F.; Bue, Mats; Kerrn-Jespersen, Sigrid; Fuursted, Kurt; Søballe, Kjeld; Birke-Sørensen, Hanne

    2014-01-01

    The relatively short half-lives of most β-lactams suggest that continuous infusion of these time-dependent antimicrobials may be favorable compared to short-term infusion. Nevertheless, only limited solid-tissue pharmacokinetic data are available to support this theory. In this study, we randomly assigned 12 pigs to receive cefuroxime as either a short-term or continuous infusion. Measurements of cefuroxime were obtained every 30 min in plasma, subcutaneous tissue, and bone. For the measurements in solid tissues, microdialysis was applied. A two-compartment population model was fitted separately to the drug concentration data for the different tissues using a nonlinear mixed-effects regression model. Estimates of the pharmacokinetic parameters and time with concentrations above the MIC were derived using Monte Carlo simulations. Except for subcutaneous tissue in the short-term infusion group, the tissue penetration was incomplete for all tissues. For short-term infusion, the tissue penetration ratios were 0.97 (95% confidence interval [CI], 0.67 to 1.39), 0.61 (95% CI, 0.51 to 0.73), and 0.45 (95% CI, 0.36 to 0.56) for subcutaneous tissue, cancellous bone, and cortical bone, respectively. For continuous infusion, they were 0.53 (95% CI, 0.33 to 0.84), 0.38 (95% CI, 0.23 to 0.57), and 0.27 (95% CI, 0.13 to 0.48) for the same tissues, respectively. The absolute areas under the concentration-time curve were also lower in the continuous infusion group. Nevertheless, a significantly longer time with concentrations above the MIC was found for continuous infusion up until MICs of 4, 2, 2, and 0.5 μg/ml for plasma and the same three tissues mentioned above, respectively. For drugs with a short half-life, like cefuroxime, continuous infusion seems to be favorable compared to short-term infusion; however, incomplete tissue penetration and high MIC strains may jeopardize the continuous infusion approach. PMID:25313214

  1. Combination of Continuous Dexmedetomidine Infusion with Titrated Ultra-Low-Dose Propofol-Fentanyl for an Awake Craniotomy.

    PubMed

    Das, Samaresh; Al-Mashani, Ali; Suri, Neelam; Salhotra, Neeraj; Chatterjee, Nilay

    2016-08-01

    An awake craniotomy is a continuously evolving technique used for the resection of brain tumours from the eloquent cortex. We report a 29-year-old male patient who presented to the Khoula Hospital, Muscat, Oman, in 2016 with a two month history of headaches and convulsions due to a space-occupying brain lesion in close proximity with the left motor cortex. An awake craniotomy was conducted using a scalp block, continuous dexmedetomidine infusion and a titrated ultra-low-dose of propofolfentanyl. The patient remained comfortable throughout the procedure and the intraoperative neuropsychological tests, brain mapping and tumour resection were successful. This case report suggests that dexmedetomidine in combination with titrated ultra-low-dose propofolfentanyl are effective options during an awake craniotomy, ensuring optimum sedation, minimal disinhibition and a rapid recovery. To the best of the authors' knowledge, this is the first awake craniotomy conducted successfully in Oman.

  2. Lung concentrations of ceftazidime administered by continuous versus intermittent infusion in patients with ventilator-associated pneumonia.

    PubMed

    Cousson, Joël; Floch, Thierry; Guillard, Thomas; Vernet, Véronique; Raclot, Pascal; Wolak-Thierry, Aurore; Jolly, Damien

    2015-04-01

    Ceftazidime is a beta-lactam compound that exerts a time-dependent bactericidal effect. Numerous arguments are in favor of continuous administration of ceftazidime, both for reasons of clinical efficacy and to preserve bacteriological mutation. We report a prospective, single-center, parallel-group, randomized, controlled trial comparing two modes of administration of ceftazidime, namely, continuous administration (loading dose of 20 mg/kg of body weight followed by 60 mg/kg/day) versus intermittent administration (20 mg/kg over 30 min every 8 h) in 34 patients with ventilator-associated pneumonia due to Gram-negative bacilli. The study was performed over 48 h with 13 and 18 assessments of serum ceftazidime in the continuous-infusion group (group A) and the intermittent-fusion group (group B), respectively. Bronchoalveolar lavage (BAL) was performed at steady state in both groups at 44 h to determine ceftazidime levels in the epithelial lining fluid. We chose a predefined threshold of 20 mg/liter for serum concentrations of ceftazidime because of ecological conditions in our center. The median time above 20 mg/liter (T>20 mg) was 100% in group A versus 46% in group B. In group A, 14/17 patients had 100% T>20 mg, versus only 1/17 patients in group B. In the epithelial lining fluid, the median concentration of ceftazidime was 12 mg/liter in group A versus 6 mg/liter in group B. A threshold of 8 mg/liter in the epithelial lining fluid was achieved twice as often in group A as in group B. This study of ceftazidime concentrations in the epithelial lining fluid indicates that continuous infusion presents advantages in terms of pharmacodynamics and predictable efficacy in patients presenting ventilator-associated pneumonia.

  3. Clinical outcomes with extended or continuous versus short-term intravenous infusion of carbapenems and piperacillin/tazobactam: a systematic review and meta-analysis.

    PubMed

    Falagas, Matthew E; Tansarli, Giannoula S; Ikawa, Kazuro; Vardakas, Konstantinos Z

    2013-01-01

    We sought to study whether the better pharmacokinetic and pharmacodynamic (PK/PD) properties of carbapenems and piperacillin/tazobactam, when the duration of infusion is longer, were associated with lower mortality. PubMed and Scopus were searched for studies reporting on patients treated with extended (≥3 hours) or continuous (24 hours) versus short-term duration (20-60 minutes) infusions of carbapenems or piperacillin/tazobactam. Fourteen studies were included (1229 patients). Mortality was lower among patients receiving extended or continuous infusion of carbapenems or piperacillin/tazobactam compared to those receiving short-term (risk ratio [RR], 0.59; 95% confidence interval [CI], .41-.83). Patients with pneumonia who received extended or continuous infusion had lower mortality than those receiving short-term infusion (RR, 0.50; 95% CI, 0.26-0.96). Data for other specific infections were not available. The available evidence from mainly nonrandomized studies suggests that extended or continuous infusion of carbapenems or piperacillin/tazobactam was associated with lower mortality. Well-designed randomized controlled trials are warranted to confirm these findings before such approaches become widely used.

  4. Insulin delivery rate into plasma in normal and diabetic subjects

    PubMed Central

    Stern, Michael P.; Farquhar, John W.; Silvers, Abraham; Reaven, Gerald M.

    1968-01-01

    Removal of insulin-131I from plasma was studied in normal and diabetic subjects with both single injection and continuous infusion of isotope techniques. Patients were studied either in the fasting state or during steady-state hyperglycemia produced by a continuous intravenous glucose infusion. Steady-state plasma insulin concentration during these studies ranged from 10 to 264 μU/ml. Labeled insulin specific activity time curves consisted of more than one exponential, indicating that a multicompartmental system for insulin metabolism exists. A mathematical technique which is applicable to non-first order processes was used to calculate the rate at which insulin was lost irreversibly from the plasma insulin pool. A direct, linear relationship was found between insulin irreversible loss rate and plasma insulin concentration over the range of concentrations studied. This linearity implies lack of saturability of the insulin removal mechanism. Since the plasma insulin pool was in a steady state during these studies, insulin irreversible loss rate was equal to the rate at which newly secreted insulin was being delivered to the general circulation. Therefore, these results indicate that changes in plasma insulin concentration result from parallel changes in the rate of insulin delivery and not from changes in the opposite direction of the rate of insulin removal. A wide range of insulin delivery rates was found among patients with similar plasma glucose concentrations, suggesting that there exists considerable variability in responsiveness to endogenous insulin among these patients. PMID:5675421

  5. The development of recurrent seizures after continuous intrahippocampal infusion of methionine sulfoximine in rats: a video-intracranial electroencephalographic study.

    PubMed

    Wang, Yue; Zaveri, Hitten P; Lee, Tih-Shih W; Eid, Tore

    2009-12-01

    Glutamine synthetase is deficient in astrocytes in the epileptogenic hippocampus in human mesial temporal lobe epilepsy (MTLE). To explore the role of this deficiency in the pathophysiology of MTLE, rats were continuously infused with the glutamine synthetase inhibitor methionine sulfoximine (MSO, 0.625 microg/h) or 0.9% NaCl (saline control) unilaterally into the hippocampus. The seizures caused by MSO were assessed by video-intracranial electroencephalogram (EEG) monitoring. All (28 of 28) of the MSO-treated animals and none (0 of 12) of the saline-treated animals developed recurrent seizures. Most recurrent seizures appeared in clusters of 2 days' duration (median; range, 1 to 12 days). The first cluster was characterized by frequent, predominantly stage I seizures, which presented after the first 9.5 h of infusion (median; range, 5.5 to 31.7 h). Subsequent clusters of less-frequent, mainly partial seizures occurred after a clinically silent interval of 7.1 days (median; range, 1.8 to 16.2 days). The ictal intracranial EEGs shared several characteristics with recordings of partial seizures in humans, such as a distinct evolution of the amplitude and frequency of the EEG signal. The neuropathology caused by MSO had similarities to hippocampal sclerosis in 23.1% of cases, whereas 26.9% of the animals had minimal neuronal loss in the hippocampus. Moderate to severe diffuse neuronal loss was observed in 50% of the animals. In conclusion, the model of intrahippocampal MSO infusion replicates key features of human MTLE and may represent a useful tool for further studies of the cellular, molecular and electrophysiological mechanisms of this disorder.

  6. Clonidine added to a continuous interscalene ropivacaine perineural infusion to improve postoperative analgesia: a randomized, double-blind, controlled study.

    PubMed

    Ilfeld, Brian M; Morey, Timothy E; Thannikary, Lisa J; Wright, Thomas W; Enneking, F Kayser

    2005-04-01

    Although clonidine has been shown to increase the duration of local anesthetic action and prolong postoperative analgesia when included in single-injection nerve blocks, the only controlled investigation of the efficacy of this practice to improve analgesia for continuous perineural local anesthetic infusion failed to discern any clinically relevant benefits. For this study, we used a larger dose of clonidine in an attempt to improve analgesia. Patients (n = 20) undergoing moderately painful orthopedic surgery of the shoulder received an interscalene brachial plexus block (40 mL of mepivacaine 1.5%, epinephrine 2.5 microg/mL, and clonidine 50 microg) and a perineural catheter before surgery. After surgery, ropivacaine 0.2% or ropivacaine 0.2% plus clonidine 2 microg/mL was delivered via the catheter for 3 days (basal rate, 5 mL/h; patient-controlled bolus, 5 mL; lockout, 1 h). Investigators and patients were blind to random group assignment. The primary outcome variable was designated as the most intense pain during the day after surgery. Secondary end-points included additional pain scores, patient-controlled bolus doses, oral analgesic use, sleep quality, and catheter- or infusion-related complications. There were no statistically significant differences between groups for any of the variables investigated. We conclude that adding clonidine 2 microg/mL to a ropivacaine interscalene perineural infusion does not decrease breakthrough pain intensity the day after surgery. For the additional end-points, our negative findings are only suggestive of a lack of effect and require further study for verification.

  7. Toward Closing the Loop: An Update on Insulin Pumps and Continuous Glucose Monitoring Systems

    PubMed Central

    Aye, Tandy; Block, Jen; Buckingham, Bruce

    2010-01-01

    Synoposis In this paper we review current pump and continuous glucose monitoring therapy and what will be required to integrate these systems into closed-loop control. Issues with sensor accuracy, lag time and calibration are discussed as well as issues with insulin pharmacodynamics which result in a delayed onset of insulin action in a closed-loop system. A stepwise approach to closed-loop therapy is anticipated where the first systems will suspend insulin delivery based on actual or predicted hypoglycemia. Subsequent systems may “control-to-range” limiting the time spent in hyperglycemia by mitigating the effects of a missed food bolus or underestimate of consumed carbohydrates while minimizing the risk of hypoglycemia. PMID:20723823

  8. Resistin's, obesity and insulin resistance: the continuing disconnect between rodents and humans.

    PubMed

    Huang, X; Yang, Z

    2016-06-01

    This review aimed to discuss the conflicting findings from resistin research in rodents and humans as well as recent advances in our understanding of resistin's role in obesity and insulin resistance. A comprehensive review and synthesis of resistin's role in obesity and insulin resistance as well as conflicting findings from resistin research in rodents and humans. In rodents, resistin is increased in high-fat/high-carbohydrate-fed, obese states characterized by impaired glucose uptake and insulin sensitivity. Resistin plays a causative role in the development of insulin resistance in rodents via 5' AMP-activated protein kinase (AMPK)-dependent and AMPK-independent suppressor of cytokine signaling-3 (SOCS-3) signaling. In contrast to rodents, human resistin is primarily secreted by peripheral-blood mononuclear cells (PBMCs) as opposed to white adipocytes. Circulating resistin levels have been positively associated with central/visceral obesity (but not BMI) as well as insulin resistance, while other studies show no such association. Human resistin has a role in pro-inflammatory processes that have been conclusively associated with obesity and insulin resistance. PBMCs, as well as vascular cells, have been identified as the primary targets of resistin's pro-inflammatory activity via nuclear factor-κB (NF-κB, p50/p65) and other signaling pathways. Mounting evidence reveals a continuing disconnect between resistin's role in rodents and humans due to significant differences between these two species with respect to resistin's gene and protein structure, differential gene regulation, tissue-specific distribution, and insulin resistance induction as well as a paucity of evidence regarding the resistin receptor and downstream signaling mechanisms of action.

  9. Use of Glucose Rate of Change Arrows to Adjust Insulin Therapy Among Individuals with Type 1 Diabetes Who Use Continuous Glucose Monitoring

    PubMed Central

    Pettus, Jeremy

    2016-01-01

    Abstract Objective: This study was performed to understand and to compare differences in utilization of continuous glucose monitoring (CGM) and the rate of change (ROC) arrow to adjust insulin therapy among individuals with type 1 diabetes (T1D), comparing those treated with multiple daily insulin injections (MDI) with those treated with continuous subcutaneous insulin infusion (CSII). Research Design and Methods: We surveyed 222 T1D individuals who regularly used real-time CGM to obtain information about general CGM use and response to glucose ROC arrows in managing their diabetes. Results: The survey was completed by 222 T1D individuals. Respondents included CSII (n = 166) and MDI (n = 56) users. MDI and CSII respondents reported similar substantial increases in correction dosages (from 220 mg/dL to 120 mg/dL) in response to increasing glucose (one ROC arrow up: rising 2–3 mg/dL/min): +120% and +108%, respectively (P = 0.13). MDI and CSII respondents reported similar substantial increases in correction dosages in response to rapidly increasing glucose (two arrows up: rising >3 mg/dL/min): +146% and +138%, respectively (P = 0.72). When correcting from 220 mg/dL to 120 mg/dL, MDI respondents reported larger correction dosage reductions than CSII respondents in response to decreasing glucose (one ROC down arrow: decreasing 2–3 mg/dL/min) and rapidly decreasing glucose (two ROC down arrows: decreasing >3 mg/dL/min): −50% versus −37%, respectively (P = 0.024) and −52% versus 38%, respectively (P = 0.034). Similar between-group differences were observed in mealtime dosage adjustments. Conclusions: CGM users often rely on ROC information when determining insulin doses and tend to make larger changes than current recommendations suggest regardless of insulin delivery method. PMID:26784128

  10. Pharmacokinetics of ceftazidime in serum and suction blister fluid during continuous and intermittent infusions in healthy volunteers.

    PubMed Central

    Mouton, J W; Horrevorts, A M; Mulder, P G; Prens, E P; Michel, M F

    1990-01-01

    The pharmacokinetics of ceftazidime were investigated during intermittent (II) and continuous (CI) infusion in eight healthy male volunteers in a crossover fashion. The total daily dose was 75 mg/kg of body weight per 24 h in both regimens, given in three doses of 25 mg/kg/8 h (II) or 60 mg/kg/24 h with 15 mg/kg as a loading dose (CI). After the third dose (II) and during CI, serum and blister fluid samples were taken. Seven new blisters were raised for each timed sample by a suction blister technique. Blisters took 90 min to form. Samples were then taken from four blisters (A samples) and 1 h later were taken from the remaining three (B samples). The concentration of ceftazidime was determined using a high-performance liquid chromatography method. After II, the concentrations in serum immediately after infusion (t = 30 min) and 8 h after the start of the infusion were 137.9 (standard deviation [SD], 27.5) and 4.0 (SD, 0.7) micrograms/ml, respectively. The half-life at alpha phase (t1/2 alpha) was 9.6 min (SD, 4.6), t1/2 beta was 94.8 min (SD, 5.4), area under the concentration-time curve (AUC) was 285.4 micrograms.h/ml (SD, 22.7), total body clearance was 0.115 liter/h.kg (SD, 0.022), and volume of distribution at steady state was 0.178 liter/kg (SD, 0.023). The blister fluid (A) samples showed a decline in concentration parallel to that of the concentrations in serum during the elimination phase with a ratio of 1:1. The t1/2 of the A samples was 96.4 min (SD, 3.2). The concentration of ceftazidime in the B blister fluid samples was significantly higher (27%) than in the A samples over time. This shows that blisters may behave as a separate compartment and establishes the need to raise new blisters for each timed sample. The mean AUC/h during continuous infusion was 21.3 micrograms . h/ml (SD, 3.0). The total body clearance was 0.113 liter/h . kg (SD, 0.018), the urinary clearance was 0.105 liter/h . kg (SD, 0.012), and the ceftazidime/creatinine clearance ratio

  11. Protein delivery with infusion pumps.

    PubMed

    Bremer, U; Horres, C R; Francoeur, M L

    1997-01-01

    When a therapeutic effect is optimized by precise control of specific temporal patterns of plasma levels, infusion offers distinct advantages over oral administration, bolus injection, or depot delivery of polypeptides. The limitations of oral delivery are well known, and although research is under way into development of carrier systems that prevent degradation of labile agents, it is unlikely that the variances in absorption will meet the need for precise control. Depot delivery from subcutaneous or intramuscular implants presents a difficult situation when local tissue reactions to the agent sometimes occur. Removal of a depot system in the event of adverse reactions presents additional difficulties. Bolus injections are unable to sustain constant plasma levels unless the drug half-life is long or the injections are frequently administered. Insulin injections, for example, would be required every 30-60 minutes to approximate the plasma levels provided by a continuous infusion; such frequent injections would not be practical on a 24-hour basis. For the developer of new polypeptides, parenteral administration offers the most direct route to the marketplace. The step from periodic injections to tightly controlled infusion is a logical progression as compared with modification of the molecules or vehicles to obtain equivalent profiles. In Table II several different types of devices that can be used for infusion of proteins are compared. Microelectronics have played a major role in the miniaturization of infusion devices and undoubtedly will continue to do so. Micromachining, a spin-off technology of integrated circuit manufacture, will also find application in small infusion devices. In the future, we will have cost-effective disposable devices (Saaman et al., 1994) built on this technology that are programmable and thus can be adapted to meet each individual therapeutic need (Horres, 1994). We can also expect to see more closed-loop drug delivery systems where

  12. Use of telemedicine in subjects with type 1 diabetes equipped with an insulin pump and real-time continuous glucose monitoring.

    PubMed

    González-Molero, Inmaculada; Domínguez-López, Marta; Guerrero, Mercedes; Carreira, Mónica; Caballero, Felix; Rubio-Martín, Eleazara; Linares, Francisca; Cardona, Isabel; Anarte, Maria Teresa; de Adana, Maria Soledad Ruiz; Soriguer, Federico

    2012-09-01

    We evaluated a telemedicine system in patients with type 1 diabetes who had optimized treatment with an insulin pump and a real-time continuous glucose monitoring system. We conducted a prospective, one-year study of 15 subjects. Three medical visits took place: pre-baseline, baseline and at 6 months. Each month the subjects transmitted information from the glucose meter, glucose sensor and insulin pump. We adjusted the treatment and returned the information by email. We evaluated psychological and metabolic variables, including HbA(1c), hypoglycaemia, hyperglycaemia and glucose variability. At baseline the mean age of the subjects was 40 years and the mean duration of diabetes was 22 years. There was a significant reduction in HbA(1c) (7.50 to 6.97%) at 6 months, a significant increase in the number of self-monitoring blood glucose checks per day (5.2 to 6.2), and significant improvements in variability: MODD, mean of daily difference (67 to 53) and MAGE, mean amplitude of glycaemic excursions (136 to 102). There were significant improvements in quality of life (92 to 87), satisfaction with the treatment (34 to 32) and less fear of hypoglycaemia (36 to 32). Adult subjects with type 1 diabetes on treatment with a continuous insulin infusion system and a real time glucose sensor and who have acceptable metabolic control and optimized treatment can benefit from the addition of a telemetry system to their usual outpatient follow-up.

  13. Continuous infusion of macrophage inflammatory protein MIP-1alpha enhances leucocyte recovery and haemopoietic progenitor cell mobilization after cyclophosphamide.

    PubMed Central

    Marshall, E.; Woolford, L. B.; Lord, B. I.

    1997-01-01

    Macrophage inflammatory protein 1alpha (MIP-1alpha) inhibits haemopoietic stem cell proliferation. This property has been exploited in a murine chemotherapy model and has been shown to ameliorate cytotoxic-induced myelosuppression after S-phase-specific cytotoxic therapy. We have now shown that BB-10010, a stable mutant of MIP-1alpha, (a) is more effective when administered as a continuous infusion than when bolus injected and (b), when administered via a 7-day infusion during and after cyclophosphamide treatment, results in an earlier recovery of leucocyte numbers. This effect was accompanied by progenitor cell mobilization into the peripheral blood and included primitive cells with marrow-repopulating ability (MRA). Maximal mobilization and recovery of leucocytes occurred when MIP-1alpha was combined with granulocyte colony-stimulating factor (G-CSF) therapy. The findings suggest that MIP1-alpha used alone or in combination with G-CSF may allow delivery of a greater chemotherapy dose intensity as a consequence of both accelerated leucocyte recovery and maintenance of high-quality mobilized progenitor cells for harvesting and peripheral blood stem cell transplantation. PMID:9192972

  14. Continuous glucose monitoring, oral glucose tolerance, and insulin - glucose parameters in adolescents with simple obesity.

    PubMed

    El Awwa, A; Soliman, A; Al-Ali, M; Yassin, M; De Sanctis, V

    2012-09-01

    In obese adolescents pancreatic beta-cells may not be able to cope with insulin resistance leading to hyperglycemia and type2 diabetes (T2DM To assess oral glucose tolerance, 72-h continuous blood glucose concentrations (CGM) and calculate homeostatic model assessment (HOMA), and the quantitative insulin sensitivity check index (QUICKI) in 13 adolescents with simple obesity (BMI SDS=4 ± 1.06). OGTT performed in 13 obese adolescents (13.47 ± 3 years) revealed 3 cases (23%) with impaired fasting glucose (IFG: fasting glucose >5.6 mmol/L), 4 cases (30%) with impaired glucose tolerance (IGT: 2h blood glucose >7.8 <11.1 mmol/L), and none with diabetes. Using the continuous glucose monitoring system ( CGMS), IFG was detected in 4 cases, the maximum serum blood glucose (BG : 2h or more after meal) was >7.8 and <11.1 mmol/L (IGT) in 9 children (69%) and >11.1 mmol/L (diabetes) in one case (7.6%). Five cases had a minimum BG recorded of <2.7 mmol/L (hypoglycemia). No glycemic abnormality was detected using HbA1C (5.7 ± 0.3%). 11/13 patients had HOMA values >2.6 and QUICKI values <0.35 denoting insulin resistance. Beta cell mass percent (B %) = 200 ± 94.8% and insulin sensitivity values (IS)=50.4 ± 45.5% denoted insulin resistance with hyper-insulinaemia and preserved beta cell mass. In obese adolescents, CGMS is superior to OGTT and HbA1C in detecting glycemic abnormalities, which appears to be secondary to insulin resistance.

  15. Rapid reversal of neuromuscular blockade by sugammadex after continuous infusion of rocuronium in patients with liver dysfunction undergoing hepatic surgery.

    PubMed

    Fujita, Ai; Ishibe, Natsuki; Yoshihara, Tatsuya; Ohashi, Jun; Makino, Hideichi; Ikeda, Mizuko; Setoguchi, Hidekazu

    2014-06-01

    Sugammadex rapidly reverses neuromuscular blockade (NMB) induced by rocuronium. NMB induced by rocuronium is prolonged in patients with liver dysfunction, because the drug is mainly excreted into the bile. However, the efficacy and safety of sugammadex in terms of reversing rocuronium-induced NMB in patients with liver dysfunction undergoing hepatic surgery have not been evaluated. This observational study investigated the efficacy and safety of sugammadex after continuous infusion of rocuronium in patients with liver dysfunction undergoing hepatic surgery. Remifentanil/propofol anesthesia was administered to 31 patients: 15 patients in the control group, and 16 patients from a group with liver dysfunction. Rocuronium (0.6 mg/kg) was administered, followed by continuous infusion. The enrolled patients were then subdivided into two groups according to the dose of sugammadex. In the first group a single dose of sugammadex (2.0 mg/kg) was given at the reappearance of the second twitch (T2). In the second group a single dose of sugammadex (4.0 mg/kg) was given at the first twitch response if T2 did not reappear in 15 minutes after stopping rocuronium. The primary outcome was time from administration of sugammadex to recovery of a train-of-four ratio to 0.9. The dose of rocuronium required in the liver dysfunction group was lower than that in the control group (6.2 vs. 8.2 μg/kg/min, p = 0.002). The mean time from the administration of sugammadex to recovery of the train-of-four ratio to 0.9 was not significantly different between the liver dysfunction group and the control group (2.2 minutes vs. 2.0 minutes in the 2 mg/kg administration group, p = 0.44 and 1.9 minutes vs. 1.7 minutes in the 4 mg/kg administration group, p = 0.70, respectively). No evidence of recurarization was observed in any of the patients. Most of the adverse events were found to be mild and such events were not related to the use of sugammadex. None of the patients was eliminated from the study

  16. Intermittent bolus injection versus continuous infusion of furosemide in normal adult greyhound dogs.

    PubMed

    Adin, Darcy B; Taylor, Aaron W; Hill, Richard C; Scott, Karen C; Martin, Frank G

    2003-01-01

    Several studies in human subjects have demonstrated greater diuresis with constant rate infusion (CRI) furosemide than intermittent bolus (IB) furosemide. This study was conducted to compare the diuretic efficacy of the same total dose of IB furosemide and CRI furosemide in 6 healthy, adult Greyhound dogs in a randomized crossover design with a 2-week washout period between treatments. For IB administration, dogs received 3 mg/kg at 0 and 4 hours. For CRI administration, dogs received a 0.66 mg/kg loading dose followed by 0.66 mg/kg/h over 8 hours. The same volume of fluid was administered for both methods. Urine output was quantified hourly. Urine electrolyte concentrations, urine specific gravity (USG), packed cell volume (PCV), total protein (TP), serum electrolyte concentrations, total carbon dioxide (TCO2), serum creatinine (sCr), and blood urea nitrogen (BUN) were determined every 2 hours. Urine production and water intake were greater (P < or = 0.05) for CRI than IB. Urine sodium and calcium losses were greater (P < 0.05) and urine potassium loss was less (P = 0.03) for CRI than IB, but there was no evidence of a difference between methods for urine magnesium and chloride losses. Serum chloride concentration was less (P < 0.001), sCr concentration greater (P = 0.04). TP greater (P = 0.01), and PCV greater (P = 0.003) for CRI than IB. No differences in USG, TCO2, BUN, or serum potassium, sodium, and magnesium concentrations were detected between methods. The same total dose of CRI furosemide resulted in more diuresis, natriuresis, and calciuresis and less kaliuresis than IB furosemide in these normal Greyhound dogs over 8 hours, suggesting that furosemide is a more effective diuretic when administered by CRI than by IB.

  17. Continuous jejunal levodopa infusion in patients with advanced parkinson disease: practical aspects and outcome of motor and non-motor complications.

    PubMed

    Eggert, Karla; Schrader, Christoph; Hahn, Michaela; Stamelou, Maria; Rüssmann, Anne; Dengler, Reinhard; Oertel, Wolfgang; Odin, Per

    2008-01-01

    We report here on the experience with continuous jejunal levodopa infusion in 13 German parkinsonian patients who have motor and nonmotor complications despite individually optimized oral treatment. The tolerability, efficacy, and the need for dose adjustment of levodopa infusion were followed-up prospectively. Thereby, we describe clinically relevant details for how to successfully initiate and handle this new treatment strategy. Thirteen patients with advanced Parkinson disease (PD) who have motor fluctuations and dyskinesia were switched off their conventional PD medication to continuous levodopa infusion and followed-up within a maximum period of 12 months. Time in "off" represented a mean of 50% (+/-14; n = 13) of awake time before levodopa infusion and was reduced to a mean of 11% (+/-9; n = 11) of awake time after 6 months. Time in "on with disabling dyskinesias" represented a mean of 17% (+/-15; n = 13) of awake time before levodopa infusion and was reduced to a mean of 3% (+/-6; n= 11) of awake time after 6 months, thereby increasing the time in good "on" state. A positive effect on nonmotor symptoms (anxiety, sleep disturbances) was also observed. In most cases, dose adjustment was required within the first 6 months (predominantly after months 1-3). The therapy was safe and effective. However, problems with the technical device were common. Continuous jejunal levodopa infusion is an effective and feasible alternative treatment option for patients with advanced PD who can cope with and tolerate the device.

  18. Postoperative Pain Management after Spinal Fusion Surgery: An Analysis of the Efficacy of Continuous Infusion of Local Anesthetics

    PubMed Central

    Reynolds, Richard A. K.; Legakis, Julie E.; Tweedie, Jillian; Chung, YoungKey; Ren, Emily J.; BeVier, Patricia A.; Thomas, Ronald L.; Thomas, Suresh T.

    2013-01-01

    Spinal fusion surgery is a major surgery that results in severe postoperative pain, therefore pain reduction is a primary concern. New strategies for pain management are currently under investigation and include multimodal treatment. A 3-year retrospective analysis of patients with idiopathic scoliosis undergoing spinal fusion surgery was performed at our hospital, assessing patient pain scores, opioid use, and recovery. We evaluated the effect of adding continuous infusion of local anesthetics (CILA) to a postoperative pain management protocol that includes intraoperative intrathecal morphine, as well as postoperative patient-controlled analgesia and oral opioid/acetaminophen combination. The study compared 25 patients treated according to the standard protocol, with 62 patients treated with CILA in addition to the pain management protocol. Patients in the CILA group used nearly 0.5 mg/kg less opioid analgesics during the first 24 hours after surgery. PMID:24436846

  19. Continuous infusion of clonidine in ventilated newborns and infants: a randomized controlled trial.

    PubMed

    Hünseler, Christoph; Balling, Gunter; Röhlig, Christoph; Blickheuser, Rainer; Trieschmann, Uwe; Lieser, Ulla; Dohna-Schwake, Christian; Gebauer, Corinna; Möller, Oliver; Hering, Fritz; Hoehn, Thomas; Schubert, Stephan; Hentschel, Roland; Huth, Ralf G; Müller, Andreas; Müller, Carsten; Wassmer, Gernot; Hahn, Moritz; Harnischmacher, Urs; Behr, Julie; Roth, Bernhard

    2014-07-01

    To assess the influence of an infusion of clonidine 1 μg/kg/hr on fentanyl and midazolam requirement in ventilated newborns and infants. Prospective, double-blind, randomized controlled multicenter trial. Controlled trials.com/ISRCTN77772144. Twenty-eight level 3 German PICUs/neonatal ICUs. Ventilated newborns and infants: stratum I (1-28 d), stratum II, (29-120 d), and stratum III (121 d to 2 yr). Patients received clonidine 1 μg/kg/hr or placebo on day 4 after intubation. Fentanyl and midazolam were adjusted to achieve a defined level of analgesia and sedation according to Hartwig score. Two hundred nineteen infants were randomized; 212 received study medication, 69.7% were ventilated in the postoperative care and 30.3% for other reasons. Primary endpoint: consumption of fentanyl and midazolam in the 72 hours following the onset of study medication (main observation period) in the overall study population. The confirmatory analysis of the overall population showed no difference in the consumption of fentanyl and midazolam. Explorative age-stratified analysis demonstrated that in stratum I (n = 112) the clonidine group had a significantly lower consumption of fentanyl (clonidine: 2.1 ± 1.8 μg/kg/hr, placebo: 3.2 ± 3.1 μg/kg/hr; p = 0.032) and midazolam (clonidine: 113.0 ± 100.1 μg/kg/hr, placebo: 180.2 ± 204.0 μg/kg/hr; p = 0.030). Strata II (n = 43) and III (n = 46) showed no statistical difference. Sedation and withdrawal-scores were significantly lower in the clonidine group of stratum I (p < 0.001). Frequency of severe adverse events did not differ between groups. Clonidine 1 μg/kg/hr in ventilated newborns reduced fentanyl and midazolam demand with deeper levels of analgesia and sedation without substantial side effects. This was not demonstrated in older infants, possibly due to lower clonidine serum levels.

  20. Ramadan fasting in diabetes patients on insulin pump therapy augmented by continuous glucose monitoring: an observational real-life study.

    PubMed

    Khalil, Ali Bernard; Beshyah, Salem A; Abu Awad, Samar M; Benbarka, Mahmoud M; Haddad, Marcil; Al-Hassan, Dana; Kahwatih, Marwa; Nagelkerke, Nico

    2012-09-01

    Hypoglycemia during the daytime of Ramadan fasting is the most feared complication of diabetes. Insulin pump therapy has been proposed as the ideal "theoretical" method for insulin delivery. We report a prospective observational, single-center study of insulin-treated patients using insulin pump therapy during Ramadan 2011. Twenty-one patients (10 males and 11 females) were selected; median age was 26 years. They adjusted their insulin as per their usual practices. Outcome measures obtained before and during Ramadan included body weight, glycosylated hemoglobin, blood glucose, total insulin dose differences, overriding tendency, suspension time during fasting, and number of hypoglycemic episodes. The patients fasted for a median of 29 days. The observed changes during Ramadan were overall not significant quantitatively, but some trends were noted. The total insulin administered during Ramadan was not different from that in the pre-Ramadan period, but there was a redistribution of insulin over a 24-h period in relation to the changes in the daily lifestyle and eating patterns. Basal insulin was decreased during the daytime by 5-20% from before Ramadan and increased during the nighttime. The mean change in the overall amount of basal insulin was not significant. A larger than usual amount of insulin bolus was given at the meals Iftar, Fowala, and Suhur; the change in the total amount of bolus insulin as a percentage change from total insulin was also not significant. No major hypoglycemic episodes were reported. Minor hypoglcemic episodes were equally distributed between daytime and nighttime and were managed by either basal insulin adjustment or suspension from the pump. This study confirms the advantages provided by insulin pump use in patients with diabetes were enhanced by the use of continuous glucose monitoring. We provided more evidence-based advice on how best to adjust the insulin pump during fasting.

  1. Combined radiotherapy, 5-fluorouracil continuous infusion and weekly oxaliplatin in advanced rectal cancer: a phase I study.

    PubMed

    François, Eric; Ychou, Marc; Ducreux, Michel; Bertheault-Cvitkovic, Frédérique; Giovannini, Marc; Conroy, Thierry; Lemanski, Claire; Thomas, Olivier; Magnin, Valérie

    2005-12-01

    The aim of this study was to determine the maximum-tolerated dose (MTD) of weekly oxaliplatin combined with 5-fluorouracil (5FU) continuous infusion administered concomitantly with fractionated radiotherapy in patients presenting advanced rectal cancer. Forty-three patients with rectal cancer (stage T3/T4 (n = 24), metastatic (n = 17) and 2 with local recurrence), were included. The radiotherapy dose delivered was 45 Gy over 5 weeks (1.8 Gy/fraction/day, 5 days per week). The initial weekly oxaliplatin dosage was 30 mg/m2 and the 5FU dosage 150 mg/m2/d. The oxaliplatin and 5FU doses were escalated. Eight dose levels were tested. At dose level 8 (oxaliplatin 80 mg/m2, 5FU 225 mg/m2/d), 2 patients out of 4 presented dose-limiting toxicity (severe diarrhoea with dehydration and fatal shock, rectovesical fistula). At dose level 7, 2 further patients presented with grade 3 diarrhoea. The main toxicity of the combination was diarrhoea. The hematological and neurological toxicities were not severe and were not dose-limiting. Out of the 30 patients undergoing surgery, 4 (13.3%) presented with pathological complete response and 4 (13.3%) only presented with microscopic residual disease. The results from this study enabled determination of the recommended weekly oxaliplatin dose (60 mg/m2) combined with 5FU continuous infusion (225 mg/m2) and fractionated radiotherapy (45 Gy) in the pre-operative treatment of advanced rectal cancer. The good safety profile of the regimen, associated with promising results in terms of histological response, suggest that the regimen could be developed in future phase II/III studies.

  2. Continuous Intraoperative Cefazolin Infusion May Reduce Surgical Site Infections During Cardiac Surgical Procedures: A Propensity-Matched Analysis.

    PubMed

    Trent Magruder, J; Grimm, Joshua C; Dungan, Samuel P; Shah, Ashish S; Crow, Jessica R; Shoulders, Bethany R; Lester, Laeben; Barodka, Viachaslau

    2015-12-01

    The authors sought to determine whether an institutional transition from intermittent to continuous dosing of intraoperative antibiotics in cardiac surgery affected surgical site infection (SSI) outcomes. A retrospective chart review utilizing propensity matching. A single academic, tertiary care hospital. One thousand one hundred seventy-nine patients undergoing coronary artery bypass grafting (CABG) and/or cardiac valvular surgery between April 2013 and November 2014 who received perioperative cefazolin. By method of cefazolin administration, patients were divided into an "intermittent-dosing" (ID) group and a "continuous-infusion" (CI) group. Of the 1,179 patients who underwent cardiac surgery during the study period, 1:1 propensity score matching yielded 399 patients in each group. Rates of diabetes (33.6% ID v 33.8% CI, p = 0.94), coronary artery bypass (62.3% v 61.4%, p = 0.66), and bilateral internal mammary artery harvesting (6.0% v 8.3%, p = 0.22) were similar between groups. SSIs occurred in more ID patients than CI patients (2.3% v 0.5%, p = 0.03). This difference was driven by decreases in extremity and conduit harvest site SSIs (1.8% v 0.3%, p = 0.03), as there were no episodes of mediastinitis, and superficial sternal SSI rates did not differ (0.5% v 0.3%, p = 0.56). There also were significantly fewer episodes of pneumonia in the CI group (6.0% v 2.3%, p = 0.008). Intensive care unit and total lengths of stay did not differ. Thirty-day mortality was 2.8% in both groups (p = 1.00). As compared to ID regimens, CI cefazolin infusion may