Adjustment Of Infusion Rate Research Articles

Model-informed precision dosing of antimicrobial drugs in pediatrics: experiences from a pilot scale program.

Antibiotics are among the most utilized drugs in pediatrics. Nonetheless, there is a lack in pharmacokinetics information for this population, and dosing criteria may vary between healthcare centers. Physiological variability associated with maturation in pediatrics makes it challenging to reach a consensus on adequate dosing, which is further accentuated in more vulnerable groups, such as critically ill or oncology patients. Model-informed precision dosing is a useful practice that allows dose optimization and attainment of antibiotic-specific pharmacokinetic/pharmacodynamic targets. The aim of this study was to evaluate the needs of model-informed precision dosing of antibiotics in a pediatrics unit, at a pilot scale. Pediatric patients under antibiotic treatment were monitored with either a pharmacokinetic/pharmacodynamic optimized sampling scheme or through opportunistic sampling. Clindamycin, fluconazole, linezolid, meropenem, metronidazole, piperacillin, and vancomycin plasma concentrations were quantified through a liquid chromatography coupled to mass spectrometry method. Pharmacokinetic parameters were estimated using a Bayesian approach to verify pharmacokinetic/pharmacodynamic target attainment. A total of 23 pediatric patients aged 2 to 16years were included, and 43 dosing regimens were evaluated; 27 (63%) of them required adjustments as follows: 14 patients were underdosed, 4 were overdosed, and 9 patients needed infusion rate adjustments. Infusion rate adjustments were mostly recommended for piperacillin and meropenem; daily doses were augmented for vancomycin and metronidazole, meanwhile linezolid was adjusted for under- and overdosing. Clindamycin and fluconazole regimens were not adjusted at all. Conclusion: Results showcase a lack of antibiotic pharmacokinetic/pharmacodynamic target attainment (particularly for linezolid, vancomycin, meropenem, and piperacillin), and the need for model-informed precision dosing in pediatrics. This study provides pharmacokinetic evidence which can further improve antibiotic dosing practices. What is Known: • Model-informed precision dosing is performed in pediatrics to optimize the treatment of antimicrobial drugs such as vancomycin and aminoglycosides, while its usefulness is debated for other groups (beta-lactams, macrolides, etc.). What is New: • Vulnerable pediatric subpopulations, such as critically ill or oncology patients, can benefit the most from model-informed precision dosing of antibiotics. • Model-informed precision dosing of linezolid, meropenem, piperacillin, and vancomycin is particularly useful in pediatrics, and further research mayimprove dosing practices altogether.

SAT-LB080 Peptide Receptor Radionuclide Therapy in Metastatic Pheochromocytoma and Paraganglioma: The Putrajaya Experience

BACKGROUND: Most metastatic pheochromocytoma (PCC) and paraganglioma (PGL) express somatostatin receptors (SSTR) similar to neuroendocrine tumors, which may benefit from peptide radionuclide receptor therapy (PRRT), a molecular targeted therapy to SSTR avid tumors. We describe 5 cases of progressive metastatic PCC/PGL who had PRRT from year 2015 to 2018. RESULTS: The patients were aged 18-51 years at diagnosis of PCC/PGL, with mean duration of disease to PRRT of 9.6 (4 - 19) years. Four patients with functional disease were on alpha-blockade prior to PRRT. All patients had surgery as first line therapy, with 3 had repeated surgeries prior to PRRT. One patient had trans-arterial chemo-embolization and one patient had alcohol ablation therapy prior PRRT. All patients underwent induction treatment of PRRT, consisting 4 cycles of Lu-177 DOTATATE given at 8-16 weeks apart, with dose ranged 68.8 - 207mCi (2.5 - 7.66 GBq). Two patients with functioning PCC/PGL experienced paroxysm during PRRT, requiring adjustment of infusion rate and anti-hypertensives. Three patients had partial response and the other 2 had mixed response at interim imaging assessment. The subsequent imaging post PRRT showed stable disease. One patient had transient worsening of disease clinically and biochemically at the treatment interim which improved with subsequent cycles of therapy. All patients with functioning disease showed improvement in symptoms and catecholamine levels upon completion of PRRT, of which, 2 of them had their antihypertensive agents stopped. CONCLUSION: PRRT helps in disease control in particularly the symptoms, blood pressure and biochemical parameters in patients with SSTR avid metastatic PCC/PGL. Further review required for long term outcome of PRRT. Unless otherwise noted, all abstracts presented at ENDO are embargoed until the date and time of presentation. For oral presentations, the abstracts are embargoed until the session begins. s presented at a news conference are embargoed until the date and time of the news conference. The Endocrine Society reserves the right to lift the embargo on specific abstracts that are selected for promotion prior to or during ENDO.

Pediatric Drug Hypersensitivity.

Pediatric drug hypersensitivity is a rapidly evolving field. The purpose of this paper is to review the current state of pediatric drug hypersensitivity and highlight new developments in diagnosis and management. This paper will discuss the safety and use of risk stratification to proceed directly to oral challenge without prior skin testing for β-lactam reactions. We review unique aspects of pediatric drug challenges and desensitizations. It is important to accurately diagnose pediatric drug hypersensitivity reactions through a detailed history, physical examination, and available diagnostic testing. Understanding of the underlying mechanism leads to appropriate classification which is necessary to direct management. The decision to perform drug challenge, desensitization, or recommend avoidance of a medication can have a significant impact on a patient's treatment. Utilization of weight-based dose and infusion rate adjustments for current drug challenge and desensitization protocols optimize success.

Safety, tolerability, pharmacokinetics, and immunogenicity of the therapeutic monoclonal antibody mAb114 targeting Ebola virus glycoprotein (VRC 608): an open-label phase 1 study

mAb114 is a single monoclonal antibody that targets the receptor-binding domain of Ebola virus glycoprotein, which prevents mortality in rhesus macaques treated after lethal challenge with Zaire ebolavirus. Here we present expedited data from VRC 608, a phase 1 study to evaluate mAb114 safety, tolerability, pharmacokinetics, and immunogenicity. In this phase 1, dose-escalation study (VRC 608), conducted at the US National Institutes of Health (NIH) Clinical Center (Bethesda, MD, USA), healthy adults aged 18-60 years were sequentially enrolled into three mAb114 dose groups of 5 mg/kg, 25 mg/kg, and 50 mg/kg. The drug was given to participants intravenously over 30 min, and participants were followed for 24 weeks. Participants were only enrolled into increased dosing groups after interim safety assessments. Our primary endpoints were safety and tolerability, with pharmacokinetic and anti-drug antibody assessments as secondary endpoints. We assessed safety and tolerability in all participants who received study drug by monitoring clinical laboratory data and self-report and direct clinician assessment of prespecified infusion-site symptoms 3 days after infusion and systemic symptoms 7 days after infusion. Unsolicited adverse events were recorded for 28 days. Pharmacokinetic and anti-drug antibody assessments were completed in participants with at least 56 days of data. This trial is registered with ClinicalTrials.gov, number NCT03478891, and is active but no longer recruiting. Between May 16, and Sept 27, 2018, 19 eligible individuals were enrolled. One (5%) participant was not infused because intravenous access was not adequate. Of 18 (95%) remaining participants, three (17%) were assigned to the 5 mg/kg group, five (28%) to the 25 mg/kg group, and ten (55%) to the 50 mg/kg group, each of whom received a single infusion of mAb114 at their assigned dose. All infusions were well tolerated and completed over 30-37 min with no infusion reactions or rate adjustments. All participants who received the study drug completed the safety assessment of local and systemic reactogenicity. No participants reported infusion-site symptoms. Systemic symptoms were all mild and present only in four (22%) of 18 participants across all dosing groups. No unsolicited adverse events occurred related to mAb114 and one serious adverse event occurred that was unrelated to mAb114. mAb114 has linear pharmacokinetics and a half-life of 24·2 days (standard error of measurement 0·2) with no evidence of anti-drug antibody development. mAb114 was well tolerated, showed linear pharmacokinetics, and was easily and rapidly infused, making it an attractive and deployable option for treatment in outbreak settings. Vaccine Research Center, US National Institute of Allergy and Infectious Diseases, and NIH.

Management of the perioperative blood glucose in neonates

The perioperative blood glucose levels are susceptible to a variety of factors in newborns.If dysglycemia occurs, it is highly likely to lead to adverse clinical outcomes.Therefore, blood glucose management properly during operation has drawn great attention in the field of neonatal anesthesia.Neonates, especially premature infants, would have impaired neurological functions, once they develop hyperglycemia or hypoglycemia during surgery.Recent studies have shown that intraoperative administration of isotonic solution containing low concentrations of dextrose, close monitoring of blood glucose and promptly adjustment of the infusion rate can improve safety and prognosis.This review describes the influencing factors of perioperative blood glucose levels, the damage of dysglycemia and the effectiveness of dextrose-containing fluid in neonates. Key words: Neonate; Perioperative period; Blood glucose; Fluid

Long-term compliance with a validated intravenous insulin therapy protocol in cardiac surgery patients: a quality improvement project.

Safe and efficient blood glucose (BG) level control after cardiac surgery relies on an intensive care unit (ICU) team-based approach, including implementation of a dynamic insulin therapy protocol (ITP). Long-term compliance with such a complex protocol is poorly addressed in the literature. The aim of this study was to assess the long-term compliance of nurses with the ITP, 7 years after its implementation in the ICU. A professional practice evaluation, integrated in a process of quality improvement program, was retrospectively conducted on 224 consecutive cardiac surgery patients over a 6-month period (PHASE 1). The timing of BG measurements and the insulin infusion rate adjustments (primary endpoints) were correctly performed according to protocol requirements in 35 and 53% of the cases, respectively. After systemic analysis of the causes of protocol deviations, four corrective measures aiming at improving both physician and nurse adherence to the protocol were implemented in the ICU. Evaluation of 104 patients in PHASE 2 showed a significant improvement in both the timing of BG measurements (83 %, P < 0.001 vs. PHASE 1), and insulin infusion rate adjustments (76%, P < 0.001). Seven years after the implementation of a dynamic insulin infusion protocol, major protocol deviations were observed. Identification of several causes after a professional practice evaluation and the implementation of simple corrective measures restored a high level of nurse compliance.

Transient and Regional Ischemia Related to Continuous Saline Solution Infusion during Radial Artery Access

This case series illustrates a radial access complication seen in 7 of 9 consecutive patients (age range, 44–53 y) undergoing uterine artery embolization in May and June 2017. Demonstrative images and videos identify a transient and clinically consequential skin ischemia caused by intraprocedural saline solution infusion through the occlusive radial artery sheath. All complications documented were classified as mild adverse events (class A) according to Society of Interventional Radiology criteria. Complication severity ranged from transient blanching to ischemic necrosis of the skin. Operator cognizance of this phenomenon with appropriate adjustment of saline solution infusion rates will prevent tissue ischemia and necrosis in radial access cases.

Thromboelastography-based anticoagulation management during extracorporeal membrane oxygenation: a safety and feasibility pilot study

BackgroundThere is no consensus on the management of anticoagulation during extracorporeal membrane oxygenation (ECMO). ECMO is currently burdened by a high rate of hemostatic complications, possibly associated with inadequate monitoring of heparin anticoagulation. This study aims to assess the safety and feasibility of an anticoagulation protocol for patients undergoing ECMO based on thromboelastography (TEG) as opposed to an activated partial thromboplastin time (aPTT)-based protocol.MethodsWe performed a multicenter, randomized, controlled trial in two academic tertiary care centers. Adult patients with acute respiratory failure treated with veno-venous ECMO were randomized to manage heparin anticoagulation using a TEG-based protocol (target 16–24 min of the R parameter, TEG group) or a standard of care aPTT-based protocol (target 1.5–2 of aPTT ratio, aPTT group). Primary outcomes were safety and feasibility of the study protocol.ResultsForty-two patients were enrolled: 21 were randomized to the TEG group and 21 to the aPTT group. Duration of ECMO was similar in the two groups (9 (7–16) days in the TEG group and 11 (4–17) days in the aPTT group, p = 0.74). Heparin dosing was lower in the TEG group compared to the aPTT group (11.7 (9.5–15.3) IU/kg/h vs. 15.7 (10.9–21.3) IU/kg/h, respectively, p = 0.03). Safety parameters, assessed as number of hemorrhagic or thrombotic events and transfusions given, were not different between the two study groups. As for the feasibility, the TEG-based protocol triggered heparin infusion rate adjustments more frequently (p < 0.01) and results were less frequently in the target range compared to the aPTT-based protocol (p < 0.001). Number of prescribed TEG or aPTT controls (according to study groups) and protocol violations were not different between the study groups.ConclusionsTEG seems to be safely used to guide anticoagulation management during ECMO. Its use was associated with the administration of lower heparin doses compared to a standard of care aPTT-based protocol.Trial registration ClinicalTrials.gov, October 22,2014. Identifier: NCT02271126.

Rituximab as a Therapeutic Option for Steroid-Sensitive Minimal Change Nephrotic Syndrome in Adults.

Minimal change nephrotic syndrome (MCNS) usually responds to steroids but frequently relapses, requiring additional treatment with immunosuppressive agents. Rituximab is a chimeric murine/human monoclonal immunoglobulin G1 antibody that targets CD20, a B-cell differentiation marker. B-cell recovery begins at approximately 6 months following the completion of treatment. Rituximab has a beneficial effect, with the sustained remission or reduction of proteinuria in patients with steroid-dependent MCNS. Relapses are thought to be associated with an increase in CD19 cells. The mean serum half-life of rituximab was reported to be 10-15 days in patients with steroid-dependent MCNS. Only infusion reactions, such as rash and chills, occurred after single-dose rituximab infusion and can be managed by pre-medication or infusion rate adjustments. Even though severe adverse effects of rituximab are not expected, we must be aware of potentially life-threatening adverse effects. Controlled randomized trials that include adult patients with steroid-dependent MCNS are required to prove the efficacy and safety of rituximab and to evaluate the cost-effectiveness of rituximab treatment. In this review, we highlight recent studies and discuss the effects of these studies on the management of patients with MCNS in adults.

Physician-Directed Versus Computerized Closed-Loop Control of Blood Pressure Using Phenylephrine in a Swine Model.

Vasopressors provide a rapid and effective approach to correct hypotension in the perioperative setting. Our group developed a closed-loop control (CLC) system that titrates phenylephrine (PHP) based on the mean arterial pressure (MAP) during general anesthesia. As a means of evaluating system competence, we compared the performance of the automated CLC with physicians. We hypothesized that our CLC algorithm more effectively maintains blood pressure at a specified target with less blood pressure variability and reduces the dose of PHP required. In a crossover study design, 6 swine under general anesthesia were subjected to a normovolemic hypotensive challenge induced by sodium nitroprusside. The physicians (MD) manually changed the PHP infusion rate, and the CLC system performed this task autonomously, adjusted every 3 seconds to achieve a predetermined MAP. The CLC maintained MAP within 5 mm Hg of the target for (mean ± standard deviation) 93.5% ± 3.9% of the time versus 72.4% ± 26.8% for the MD treatment (P = .054). The mean (standard deviation) percentage of time that the CLC and MD interventions were above target range was 2.1% ± 3.3% and 25.8% ± 27.4% (P = .06), respectively. Control statistics, performance error, median performance error, and median absolute performance error were not different between CLC and MD interventions. PHP infusion rate adjustments by the physician were performed 12 to 80 times in individual studies over a 60-minute period. The total dose of PHP used was not different between the 2 interventions. The CLC system performed as well as an anesthesiologist totally focused on MAP control by infusing PHP. Computerized CLC infusion of PHP provided tight blood pressure control under conditions of experimental vasodilation.

The impact of pharmacy monitoring and intervention in patients receiving intravenous heparin.

Background Intravenous unfractionated heparin (IV UFH) has a narrow therapeutic index and poses a high risk of bleeding. Objective To determine the impact of pharmacy monitoring and intervention on adherence to and appropriate implementation of IV UFH protocol. Setting A 438 bed hospital specializing in cardiac services. Methods This is a retrospective chart review study. Pre-pharmacy intervention data were collected from November 2013 to January 2014 and compared to post-pharmacy intervention data obtained between August 2014 and October 2014. Patients were included if they received IV UFH for at least 24hours. The first three daytime laboratory draws were collected for each patient and analyzed using generalized estimating equations to quantify the association between pharmacy monitoring and adherence to the institution's protocol. Main outcome measures Designation of appropriate protocol, accurate selection of initial infusion rate, timing of anti-Xa levels within 60min of anticipated due time, change of infusion rate within 120min of laboratory result, and appropriate adjustment of infusion rates. Results A total of 195 data points were included. The initial selection of infusion rate and subsequent adjustments were more appropriate in the post-intervention period with an odds ratio of 8.36 (95% CI 2.41-29.01, p value=0.0008), and 4.66 (95% CI 1.41-15.43, p value=0.0118), respectively. Conclusion The results of this study indicate that pharmacy monitoring of IV UFH therapy has improved adherence to an institution's protocol and is associated with more accurate selection of initial infusion rates and adjustment of infusions based upon laboratory results.

Rationale for and design of the TRUE-AHF trial: the effects of ularitide on the short-term clinical course and long-term mortality of patients with acute heart failure.

NCT01661634.

Total intravenous anaesthesia using propofol and sufentanil allows controlled long-term ventilation in rabbits without neuromuscular blocking agents.

The aim of this study was to evaluate a total intravenous anaesthesia (TIVA) protocol using propofol and sufentanil without neuromuscular blocking agents (NBAs) for a non-recovery lung pathology study in rabbits including 10 h of pressure-controlled ventilation. TIVA was started with 20 mg/kg/h propofol and 0.5 µg/kg/h sufentanil. The depth of anaesthesia was assessed by reflex testing and monitoring of spontaneous movements or respiratory efforts. Vital parameters were monitored to assess the effects of the TIVA protocol. The infusion rates were increased whenever reflex testing indicated inadequate depth of anaesthesia, and were reduced when vital parameters indicated unnecessarily deep levels. Median infusion rates of 35 mg/kg/h propofol and 2.0 µg/kg/h sufentanil were needed to ensure an adequate depth of anaesthesia. This protocol suppressed spontaneous movements, breathing and palpebral reflexes, but was unable to suppress corneal and pedal withdrawal reflexes. Since significant drops in arterial blood pressure (ABP) were observed and the animals were not exposed to painful procedures, positive corneal and pedal withdrawal reflexes were tolerated. In conclusion, propofol and sufentanil is a suitable combination for long-term anaesthesia in non-recovery lung pathology models in rabbits without painful procedures. ABP must be monitored carefully because of the circulatory side-effects, but it is an inappropriate surrogate marker for depth of anaesthesia. Due to the lack of neuromuscular blockade this TIVA protocol allows the adjustment of infusion rates based on reflex testing. The resulting decreased risk of unnoticed awareness is a decisive refinement in anaesthesia for similar studies including long-term mechanical ventilation in rabbits.

Application of enteral nutrition in pediatric surgery

To explore the value and safety of the application of enteral nutrition in pediatric surgery. Clinical data of 56 children patients who could not undertake oral feeding or those who required enteral nutrition by nasojejunal tube over 7 days in our ward from June 2007 to May 2013 were retrospectively analyzed. Children younger than one year old received enteral nutritional formulation Ai Er Shu mainly composed of short peptides or amino acids, and children over one year received Small peptide or Nengquansu mainly composed of short peptide. Among these 56 children patients, primary disease was pancreatitis in 20 cases, lacerated wound in 10, duodenal perforation in 6, duodenal septum-shape stenosis in 9, annular pancreas in 6, and hepatoblastoma in 5. All the patients successfully completed the enteral nutrition therapy within 7-37 (18±9.9) days with good recovery. During the treatment, 5 cases (8.9%) developed diarrhea, 3 cases (5.4%) nausea and vomiting, 2 cases (3.6%) mild abdominal distension, 5 cases(8.9%) mild abdominal pain, and the symptoms were relieved after adjustment of nutrient solution concentration and infusion rate. After enteral nutrition for 10 days, the nutritional status of children was improved, and weight, blood red cell count, hemoglobin, serum albumin, prealbumin increased significantly (P<0.05). Application of enteral nutrition in pediatric surgery is safe and effective, which can improve the nutritional status of children and promote the recovery.

Intravenous lidocaine for neuropathic pain: a retrospective analysis of tolerability and efficacy.

This study was designed to describe the efficacy and toxicity of intravenous (i.v.) lidocaine infusions for the treatment of neuropathic pain initially administered at a flat-rate trial dose of 500 mg over 30 minutes. Academic, tertiary care hospital and infusion center. Data were retrospectively collected and analyzed for efficacy, correlations between infusion rates with adverse effects, patterns of infusion rate adjustments, and infusion frequencies. The average rate for all infusions was 9.1 mg/min. Efficacy was seen in 45 patients (65%), and all but eight patients (12%) required infusion rate reductions from the initial test rate of 16.7 mg/min due to adverse effects. Fifty-five patients experienced adverse effects, with light-headedness as the most frequently reported side effect. The flat-dose trial used under the University of Wisconsin Health protocol for i.v. lidocaine administration did not cause serious adverse events, but few patients who responded to this trial dose tolerated subsequent infusions at the trial rate. Due to the lack of serious adverse events, administering an aggressive trial dose to elicit an analgesic response appears to be rational. If patients show a benefit from the trial dose, the need for reductions in infusion rate of subsequent doses should be anticipated.

Adjustment of basal insulin infusion rate in T1DM by hybrid PSO

Basal insulin infusion rate which should be adjusted to increase or decrease insulin delivery with the varying blood sugar level plays a key role in type 1 diabetes mellitus (T1DM) patients for maintaining the blood glucose level approximately steady within reference range in order to avoid the complications developed from diabetes. This paper proposes an effective hybrid particle swarm optimization (HPSO) algorithm for solving the basal insulin infusion rate problem. In HPSO, bad experience lesson learning scheme and local search based on chaotic dynamics are proposed to make a good balance between global exploration and local exploitation. Simulation results based on a set of well-known optimization benchmark instances and the basal insulin infusion rate adjustment problem for T1DM demonstrate the effectiveness of the proposed HPSO. In silico tests on standard virtual subject via HPSO show that under nominal condition the blood glucose concentrations could be kept within a range of 80---150 mg/dL within less than 5 days; meanwhile, in case of random variations in meal timings within $$\pm $$±60 min or meal amounts within $$\pm $$±75 % deviation from the nominal values, the blood glucose concentrations could be kept within the safe regions.

Decreased Morbidity and Mortality in DKA Over Time

Research Article| December 01 2013 Decreased Morbidity and Mortality in DKA Over Time AAP Grand Rounds (2013) 30 (6): 70. https://doi.org/10.1542/gr.30-6-70 Views Icon Views Article contents Figures & tables Video Audio Supplementary Data Peer Review Share Icon Share Twitter LinkedIn Tools Icon Tools Get Permissions Cite Icon Cite Search Site Citation Decreased Morbidity and Mortality in DKA Over Time. AAP Grand Rounds December 2013; 30 (6): 70. https://doi.org/10.1542/gr.30-6-70 Download citation file: Ris (Zotero) Reference Manager EasyBib Bookends Mendeley Papers EndNote RefWorks BibTex toolbar search nav search search input Search input auto suggest search filter All PublicationsAll JournalsAAP Grand RoundsPediatricsHospital PediatricsPediatrics In ReviewNeoReviewsAAP NewsAll AAP Sites Search Advanced Search Topics: diabetic ketoacidosis Source: White PC, Dickson BA. Low morbidity and mortality in children with diabetic ketoacidosis treated with isotonic fluids. J Pediatr. 2013; 163(3): 761– 766; doi: https://doi.org/10.1016/j.jpeds.2013.02.005Google Scholar Investigators from the University of Texas Southwestern conducted a retrospective study to assess the rate of cerebral edema (CE) in children with diabetic ketoacidosis (DKA) treated with a specific protocol. A major feature of the protocol was use of a “two bag method” of intravenous (IV) fluid administration (both bags contained isotonic electrolyte concentrations, and one included 10% dextrose), allowing rapid bedside adjustment of glucose infusion rate. Fluid administration typically ranged from 2 to 2.5 times maintenance rates. Administrative databases and medical records were queried to identify children hospitalized with DKA at a single institution between 1999 and 2011. Clinical and demographic data of study children were abstracted from the medical records. The presence of CE was defined either by a positive CT scan or documented treatment for altered mental status other than routine DKA management. Clinical features of children with and without CE were compared. The investigators also measured the rate of death in admissions for DKA and/or neurologic sequelae at discharge. To assess compliance with the standard protocol, the investigators reviewed randomly selected medical records of 100 admissions in children with DKA; 66 admissions were managed in accordance with the protocol. Data were analyzed on 3,712 admissions for DKA in 2,436 unique patients. Three hundred forty-eight admissions were treated in the ICU and 229 had a head CT. Twenty admissions met the study definition of CE (0.5%). Children with CE had significantly worse acidosis (median pH 7.07 vs 7.25) and more severe hyperglycemia (median initial glucose 530 vs 339 mg/dL) than those without this complication. CE was significantly associated with multiple admissions in the same patient for DKA. One study patient (without CE) died, and neurologic sequelae were reported in 2 patients (one of whom had CE), for an overall death or disability rate of 0.08%. The authors conclude that, compared with recently reported data in children with DKA (death or disability in 0.3%1 ), use of the DKA protocol used at their institution is associated with extremely low rates of morbidity and mortality. Dr Sweney has disclosed no financial relationship relevant to this commentary. This commentary does not contain a discussion of an unapproved/investigative use of a commercial product/device. DKA continues to complicate care of children with type 1 diabetes. Risk factors for DKA include: teen years, female gender, low economic status, insulin pump malfunction, poor glycemic control, and a concurrent psychiatric disorder.2 CE is the most serious complication, and clinically apparent CE complicates up to 1% of DKA admissions. Serial imaging studies suggest that the majority of children have smaller ventricular spaces or “subclinical” brain edema3 during the acute illness as compared to their baseline, but the mechanism by which subclinical brain swelling changes to clinical brain swelling remains uncertain. Unfortunately, those with clinical signs of... You do not currently have access to this content.

Low Morbidity and Mortality in Children with Diabetic Ketoacidosis Treated with Isotonic Fluids

To assess current rates of complications of diabetic ketoacidosis (DKA), particularly cerebral edema, in a large tertiary-care pediatric hospital with a consistent management protocol. We report our single-center retrospective experience with 3712 admissions with DKA in 1999-2011. Our DKA protocol features a "3-bag" system using 2 bags of rehydration fluids, identical except for the presence in 1 bag of 10% dextrose, to allow rapid adjustment of glucose infusion rate. The third bag contains insulin. Fluids are administered at a total rate of 2-2.5 times "maintenance" fluid requirements. Total electrolyte concentration is kept approximately isotonic. Billing and medical records databases at Children's Medical Center Dallas were examined for cases of DKA, cerebral edema, other morbidities, and death. We ascertained 20 cases of cerebral edema (0.5%). Most presented early (median duration of treatment 2 hours). Only 10 of 20 computed tomography scans were graded as moderate edema or worse. Only 10 patients received treatment other than routine DKA management. There was 1 death in a patient with sickle cell trait who developed intravascular sickling. Two patients had neurologic sequelae at hospital discharge but both recovered fully. Compared with data in recent consensus statements, the Dallas protocol is associated with extremely low rates of death and disability (0.08% vs 0.3%) from DKA.

An intravenous insulin protocol for strict glycemic control in acute ischaemic stroke

There is a J-shaped association between admission glycemia and outcome. We designed an intravenous insulin protocol aiming at rapid and strict glucose control in hyperglycemic ischaemic stroke patients. Here, we describe the initial experience, safety, and efficacy of this protocol to achieve and maintain euglycemia in the first 48h. The protocol is based on parallel scales for adjustment of insulin infusion rate according to current glycemia and the rate of change of glycemia, which was recommended in our stroke unit in 4/2007 in acute ischaemic stroke patients with glycemia >6mM. Data were registered in the Acute Stroke Registry and Analysis of Lausanne (ASTRAL). Capillary blood glycemia was measured hourly with fingerprick test at onset of treatment and after each scale change. Target glycemia was 4.0-6.0mM pre-prandially (5.5-8.0mM post-prandially). Hypokalemia was defined as serum potassium <3.5mM and measured every 12h. Specific algorithms were employed during meals and for patients leaving temporarily the stroke unit for diagnostic or therapeutic workup. In the 90 protocol patients, the first normoglycemia was achieved within 8h of treatment in 91.1% of patients (median interval 4h (interquartile range (IQR): 3-6). During the median treatment duration of 25.5h (IQR: 19.7-37.7), median glucose reduction was 2.5mM (IQR: 1.3-4.3mM). The overall rate of hypoglycemias was 4.5% and hypokalemias 18.5%. There was a significant increase in the proportion of hypokalemias on the first on-treatment measurement compared to admission (24.4% vs. 8.9%, P=0.002). The proposed intravenous insulin protocol controls acute post-stroke hyperglycemia but frequently leads to hypokalemia. This issue needs to be addressed for the protocol to be suitable for use in larger, randomized controlled trial to explore its clinical effect.

Rituximab and minimal change nephrotic syndrome: a therapeutic option

Minimal change nephrotic syndrome (MCNS) usually responds to steroids but frequently relapses, requiring additional treatment with immunosuppressive agents. Rituximab is a chimeric murine/human monoclonal immunoglobulin G1 antibody that targets CD20, a B-cell differentiation marker. B-cell recovery begins at approximately 6months following the completion of treatment. Rituximab has a beneficial effect, with the sustained remission or reduction of proteinuria in patients with steroid-dependent MCNS. Relapses are thought to be associated with an increase in CD19 cells. The mean serum half-life of rituximab was reported to be 10-15days in patients with steroid-dependent nephrotic syndrome. Only infusion reactions, such as rash and chills, occurred after single-dose rituximab infusion and can be managed by pre-medication or infusion rate adjustments. Even though severe adverse effects of rituximab are not expected, physicians must be aware of potentially life-threatening adverse effects. Controlled randomized trials that include adult patients with steroid-dependent or steroid-resistant MCNS are required to prove the efficacy and safety of rituximab and to evaluate the cost-effectiveness of rituximab treatment.