Continuous Infusion Administration Research Articles

Excellent Tolerability of Ifosfamide and Mesna Via Continuous Infusion in a Pediatric Patient Population.

Ifosfamide is an antitumor agent with activity against various malignancies in pediatric patients. As a prodrug, ifosfamide requires metabolic activation, which occurs via a saturable, multistep equilibrium-based process. Due to these metabolic characteristics, the method of administration can affect its therapeutic and toxic effects. This single-center, retrospective review describes the tolerability of continuous infusion and bolus administration of ifosfamide in 10 pediatric patients with Ewing sarcoma. The primary objective was to report the hematologic toxicities of patients with differing administration methods. Secondary objectives included collecting information on nonhematologic toxicities and incidence of treatment delays and dose reductions. Ultimately, 48 cycles of ifosfamide were administered as bolus administration and 24 as continuous infusion. Patients receiving bolus administration had lower hemoglobin and platelet nadirs resulting in more transfusions and treatment delays when compared proportionally to continuous infusion. With the results of this case series, continuous infusion ifosfamide appears to be safe and feasible for outpatient administration and may offer an advantage from a hematologic adverse event profile but would need to be confirmed in a larger cohort.

Mechanisms, Characteristics, and Treatment of Neuropathic Pain and Peripheral Neuropathy Associated with Dinutuximab in Neuroblastoma Patients.

Prognosis of metastatic neuroblastoma is very poor. Its treatment includes induction chemotherapy, surgery, high-dose chemotherapy, radiotherapy, and maintenance with retinoic acid, associated with the anti-GD2 monoclonal antibody (ch14.18) dinutuximab. Immunotherapy determined a significant improvement in survival rate and is also utilized in relapsed and resistant neuroblastoma patients. Five courses of dinutuximab 100 mg/m2 are usually administered as a 10-day continuous infusion or over 5 consecutive days every 5 weeks. Dinutuximab targets the disialoganglioside GD2, which is highly expressed on neuroblastoma cells and minimally present on the surface of normal human neurons, peripheral pain fibers, and skin melanocytes. Anti GD2 antibodies bind to surface GD2 and determine the lysis of neuroblastoma cells induced by immune response via the antibody-dependent cellular cytotoxicity and the complement-dependent cytotoxicity. Dinutuximab has significant side effects, including neuropathic pain, peripheral neuropathy, hypersensitivity reactions, capillary leak syndrome, photophobia, and hypotension. The most important side effect is neuropathic pain, which is triggered by the same antibody–antigen immune response, but generates ectopic activity in axons, which results in hyperalgesia and spontaneous pain. Pain can be severe especially in the first courses of dinutuximab infusion, and requires the administration of gabapentin and continuous morphine infusion. This paper will focus on the incidence, mechanisms, characteristics, and treatment of neuropathic pain and peripheral neuropathy due to dinutuximab administration in neuroblastoma patients.

Pharmacokinetics of perioperative FVIII in adult patients with haemophilia A: An external validation and development of an alternative population pharmacokinetic model.

Haemophilia A patients require perioperative clotting factor replacement to limit excessive bleeding. Weight-based dosing of Factor VIII (FVIII) does not account for inter-individual pharmacokinetic (PK) variability, and may lead to suboptimal FVIII exposure. To perform an external validation of a previously developed population PK (popPK) model of perioperative FVIII in haemophilia A patients. A retrospective chart review identified perioperative haemophilia A patients at the University of North Carolina (UNC) between April 2014 and November 2019. Patient data was used to externally validate a previously published popPK model proposed by Hazendonk. Based on these validation results, a modified popPK model was developed to characterize FVIII PK in our patients. Dosing simulations were performed using this model to compare FVIII target attainment between intermittent bolus (IB) and continuous infusion (CI) administration methods. A total of 521 FVIII concentrations, drawn from 34 patients, were analysed. Validation analyses revealed that the Hazendonk model did not fully capture FVIII PK in the UNC cohort. Therefore, a modified one-compartment model, with weight and age as covariates on clearance (CL), was developed. Dosing simulations revealed that CI resulted in improved target attainment by 16%, with reduced overall FVIII usage by 58IU/kg, compared to IB. External validation revealed a previously published popPK model of FVIII did not adequately characterize UNC patients, likely due to differences in patient populations. Future prospective studies are needed to evaluate our model prior to implementation into clinical practice.

Evaluation of Prolonged Versus Continuous Infusions of Piperacillin/Tazobactam During Shortages of Small Volume Parenteral Solutions

Background: In 2017, a national drug shortage of small volume solutions significantly affected the preparation of intravenous antibiotics. In response, a continuous infusion administration protocol for piperacillin/tazobactam (PIP/TAZ) was implemented. Objective: To compare the outcomes of continuous to prolonged infusions of PIP/TAZ in the setting of drug shortages. Methods: This study is a single-center, retrospective cohort study in a community hospital of patients 18 years and older who received intravenous PIP/TAZ through 2 different dosing strategies of intravenous antibiotics from December 2016 to January 2018. Data were collected for 2 months on patients receiving prolonged infusions of PIP/TAZ prior to November 2017 and for 2 months on patients receiving continuous infusions of PIP/TAZ after November 2017. Results: A total of 90 patients who received PIP/TAZ via either prolonged (n = 47) or continuous infusion (n = 43) were evaluated. There were no differences between the groups in mortality (3 vs 2 deaths, P = 1.00), length of therapy (6 ± 4 vs 6 ± 3 days, P = .86), or length of stay (9 ± 7 vs 8 ± 6 days, P = .47). Additionally, no differences were noted between incidences of thrombocytopenia ( P = .41), Clostridioides difficile infection ( P = .48), acute renal failure ( P = 1.00), seizures ( P = 1.0), or 30-day readmission rates ( P = .27). Conclusions: Administration of continuous infusion PIP/TAZ appears to be a viable mitigation strategy during small volume fluid shortages. Future cost-effectiveness studies may provide information on the financial impact of continuous infusions during costly drug shortages.

Compliance with status epilepticus management protocol and effect on clinical outcomes in children with status epilepticus

BackgroundGuidelines for the management of status epilepticus (SE) aid in rationalising the treatment for a better clinical outcome; however, published literature regarding the use of antiepileptics and compliance is limited,...

Perioperative pharmacokinetic-guided factor VIII concentrate dosing in haemophilia (OPTI-CLOT trial): an open-label, multicentre, randomised, controlled trial

Dosing of replacement therapy with factor VIII concentrate in patients with haemophilia A in the perioperative setting is challenging. Underdosing and overdosing of factor VIII concentrate should be avoided to minimise risk of perioperative bleeding and treatment costs. We hypothesised that dosing of factor VIII concentrate on the basis of a patient's pharmacokinetic profile instead of bodyweight, which is standard treatment, would reduce factor VIII consumption and improve the accuracy of attained factor VIII levels. In this open-label, multicentre, randomised, controlled trial (OPTI-CLOT), patients were recruited from nine centres in Rotterdam, Groningen, Utrecht, Nijmegen, The Hague, Leiden, Amsterdam, Eindhoven, and Maastricht in The Netherlands. Eligible patients were aged 12 years or older with severe or moderate haemophilia A (severe haemophilia was defined as factor VIII concentrations of <0·01 IU/mL, and moderate haemophilia as 0·01-0·05 IU/mL), without factor VIII inhibitors, and planned for elective low or medium risk surgery as defined by surgical risk score. Patients were randomly assigned (1:1) using a web-based randomisation system and treatment minimisation, stratified by method of administration of factor VIII concentrate (continuous infusion vs bolus administration) and risk level of surgery (low and medium risk surgery), to the pharmacokinetic-guided or standard treatment group. The primary endpoint was total amount of infused factor VIII concentrate (IU per kg bodyweight) during perioperative period (from day of surgery up to 14 days after surgery). Analysis was by intention to treat and the safety analysis population comprised all participants who underwent surgery with factor VIII concentrate. This study is registered with the Netherlands Trial Registry, NL3955, and is now closed to accrual. Between May 1, 2014, and March 1, 2020, 98 patients were assessed for eligibility and 66 were enrolled in the trial and randomly assigned to the pharmacokinetic-guided treatment group (34 [52%]) or the standard treatment group (32 [48%]). Median age was 49·1 years (IQR 35·0 to 62·1) and all participants were male. No difference was seen in consumption of factor VIII concentrate during the perioperative period between groups (mean consumption of 365 IU/kg [SD 202] in pharmacokinetic-guided treatment group vs 379 IU/kg [202] in standard treatment group; adjusted difference -6 IU/kg [95% CI -88 to 100]). Postoperative bleeding occurred in six (18%) of 34 patients in the pharmacokinetic-guided treatment group and three (9%) of 32 in the standard treatment group. One grade 4 postoperative bleeding event occurred, which was in one (3%) patient in the standard treatment group. No treatment-related deaths occurred. Although perioperative pharmacokinetic-guided dosing is safe, it leads to similar perioperative factor VIII consumption when compared with standard treatment. However, pharmacokinetic-guided dosing showed an improvement in obtaining factor VIII concentrations within the desired perioperative factor VIII range. These findings provide support to further investigation of pharmacokinetic-guided dosing in perioperative haemophilia care. Dutch Research Council (NWO)-ZonMw and Takeda.

Continuous infusion versus intermittent administration of meropenem in critically ill patients (MERCY): A multicenter randomized double-blind trial. Rationale and design

ObjectiveMeropenem is a β-lactam, carbapenem antibacterial agent with antimicrobial activity against gram-negative, gram-positive and anaerobic micro-organisms and is important in the empirical treatment of serious infections in Intensive Care Unit (ICU) patients. Multi-drug resistant gram-negative organisms, coupled with scarcity of new antibiotic classes, forced healthcare community to optimize the therapeutic potential of available antibiotics. Our aim is to investigate the effect of continuous infusion of meropenem against bolus administration, as indicated by a composite outcome of reducing death and emergence of extensive or pan drug-resistant pathogens in a population of ICU patients. DesignDouble blind, double dummy, multicenter randomized controlled trial (1:1 allocation ratio). SettingTertiary and University hospitals. Interventions600 ICU patients with sepsis or septic shock, needing by clinical judgment antibiotic therapy with meropenem, will be randomized to receive a continuous infusion of meropenem 3 g/24 h or an equal dose divided into three daily boluses (i.e. 1g q8h). MeasurementsThe primary endpoint will be a composite outcome of reducing death and emergence of extensive or pan drug-resistant pathogens. Secondary endpoints will be death from any cause at day 90, antibiotic-free days at day 28, ICU-free days at day 28, cumulative SOFA-free (Sequential Organ Failure Assessment) score from randomization to day 28 and the two, separate, components of the primary endpoint. We expect a primary outcome reduction from 52 to 40% in the continuous infusion group. ConclusionsThe trial will provide evidence for choosing intermittent or continuous infusion of meropenem for critically ill patients with multi-drug resistant gram-negative infections.

Comparison of two different methods for labor analgesia depending on the mode of epidural infusion administration (continuous or intermittent)

Introduction: The use of a local anesthetic solution with opioids as a continuous epidural infusion administration during labor is controversial. It is considered to prolong the second stage of labor and to increase the total delivered dose of anesthetic, without improving the analgesia in comparison with the usage of the same solution in intermittent bolus doses, periodically. This study is designed to compare these two techniques. Materials and methods: In this study, 60 parturient women were included. Labor analgesia started with a single bolus dose of 10 mL ropivacaine 0.1% administered epidurally in both groups. Group A was, subsequently, given epidurally Ropivacaine 0.15% with Fentanyl 2 μgr/mL in continuous infusion with a rate of 10 mL/h throughout labor, while Group B was given the same dose per hour but in two bolus doses of 5 mL administered every 30 min. In both groups, we had the possibility of additional bolus doses of 5 mL of the same solution with a lock out interval of 20 min. The total dosage received, the duration of the 2nd stage of labor, the method of delivery (assisted or not, Cesarean section), the motor activity (using the Bromage scale) and the pain intensity (using the VAS 1–10, every 20 min) were evaluated. Results: No statistically significant differences were observed in the duration of labor (one way ANOVA), in the Bromage score and in the method of delivery between the two groups (x2 test). No differences were also observed in the recordings of pain intensity between the two groups (two-way ANOVA for repeated measurements), but in some specific instances Group A presented higher VAS score, although the total dosage of local anesthetic received was greater in this group compared to group B (180 mL vs. 162 mL, p = 0.04). Conclusions: The use of intermittent epidural bolus doses compared to a continuous infusion technique is associated with lower total consumption and periodically better pain management.

Comparison of two different local anesthetic infusion methods (with or without opioids) for epidural analgesia after cesarean section delivery

Aim: The aim of this study was to compare the efficacy and safety between ropivacaine 0.25% and ropivacaine 0.2% combined with a 0.025 mg/kg morphine regimen, administered as a continuous epidural infusion for analgesia after cesarean section delivery. Materials and methods: We compared 55 parturient women undergoing a cesarean section delivery with a combined spinal-epidural technique. All women received intrathecally 2–2.3 mL ropivacaine 0.75% combined with 0.3 mL fentanyl through a G27 needle. An epidural catheter was inserted immediately after spinal anesthesia. Two hours after the onset of spinal anesthesia a ropivacaine 0.25% continuous epidural infusion (7 mL/h) was administered in group A whereas a ropivacaine 0.2% combined with 0.025 morphine epidural infusion (7 mL/h) was administered in group B. The degree of motor and sensory block (using a Bromage and VAS score 1–10) were evaluated immediately after, 2 h, 4 h, 8 h and 12 h after the onset of continuous epidural infusion administration. We also evaluated all patients’ blood pressure (BP) and heart rate at the same time intervals. Results: There were no statistically significant differences in hemodynamic parameters, sensory block or analgesic effect between the groups however there were differences in motor block (Bromage score in group A 0.7 ± 0.5 vs 0.2 ± 0.4 in group B, p = 0.002). Conclusion: The use of a local anesthetic and morphine combination in group B provided efficient epidural analgesia accomplishing a lower motor blockade compared to group A.

Impact of interoperability of smart infusion pumps and an electronic medical record in critical care.

To describe the benefits of smart infusion pump interoperability with an electronic medical record (EMR) system in an adult intensive care unit (ICU) setting. In order to assess the impact of smart infusion pump and EMR interoperability, we observed whether there were changes in the frequency of electronic medication administration record (eMAR) documentation of dose titrations in epinephrine and norepinephrine infusions in the ICU setting. As a secondary endpoint, we examined whether smart pump/EMR interoperability had any impact on the rate of alerts triggered by the dose-error reduction software. Pharmacist satisfaction was measured to determine the impact of smart pump/EMR interoperability on pharmacist workflow. In the preimplementation phase, there were a total of 2,503 administrations of epinephrine and norepinephrine; 13,299 rate changes were documented, for an average of 5.31 documented rate changes per administration. With smart pump interoperability, a total of 13,024 rate changes were documented in association with 1,401 administrations, for an average of 9.29 documented rate changes per administration (a 74.9% increase). A total of 1,526 dose alerts were triggered in association with 76,145 infusions in the preimplementation phase; there were 820 dose alerts associated with 48,758 autoprogammed infusions in the postimplementation phase (absolute difference, -0.32%). ICU pharmacists largely agreed (75% of survey respondents) that the technology provided incremental value in providing patient care. Interoperability between the smart pump and EMR systems proved beneficial in the administration and monitoring of continuous infusions in the ICU setting. Additionally, ICU pharmacists may be positively impacted by improved clinical data accuracy and operational efficiency.

Continuous Versus Intermittent Infusion of Vancomycin and the Risk of Acute Kidney Injury in Critically Ill Adults: A Systematic Review and Meta-Analysis.

Critically ill patients routinely receive vancomycin as empiric antibiotic therapy. A continuous infusion administration strategy may be superior to intermittent infusion by minimizing peak concentrations and variability thereby optimizing safety. We performed a systematic review and meta-analysis to investigate the impact of vancomycin infusion strategy on acute kidney injury in critically ill adults. A systematic search of MEDLINE, CINAHL, Web of Science, International Pharmaceutical Abstracts, and Google Scholar was undertaken. We included randomized controlled trials and observational studies evaluating acute kidney injury in critically ill adults comparing vancomycin administered by intermittent and continuous infusion. Secondary outcomes included mortality and pharmacokinetic target attainment. Eleven studies were identified for analysis with baseline demographics, endpoints, protocol definitions, and outcomes extracted. When compared with intermittent infusion, continuous infusion was associated with a reduction in acute kidney injury in critically ill adults (odds ratio, 0.47; 95% CI, 0.34-0.65) and a 2.6 greater odds of pharmacokinetic target attainment (odds ratio, 2.63; 95% CI, 1.52-4.57). No difference in mortality was observed (odds ratio, 1.04; 95% CI, 0.80-1.35). When administered via a continuous infusion, vancomycin is associated with a 53% reduction in the odds of acute kidney injury and a 2.6-fold higher odds of pharmacokinetic target attainment when compared with intermittent infusion without influencing overall mortality.

Continuous regional arterial infusion versus intravenous administration of the protease inhibitor nafamostat mesilate for predicted severe acute pancreatitis: a multicenter, randomized, open-label, phase 2 trial

BackgroundContinuous regional arterial infusion (CRAI) of protease inhibitor nafamostat mesilate (NM) is used in the context of predicted severe acute pancreatitis (SAP) to prevent the development of pancreatic necrosis. Although this therapy is well known in Japan, its efficacy and safety remain unclear.MethodsThis investigator-initiated and -driven, multicenter, open-label, randomized, controlled trial (UMIN000020868) enrolled 39 patients with predicted SAP and low enhancement of the pancreatic parenchyma on computed tomography (CT). Twenty patients were assigned to the CRAI group, while 19 served as controls and were administered NM at the same dose intravenously (IV group). The primary endpoint was the development of pancreatic necrosis as determined by CT on Day 14, judged by blinded central review.ResultsThere was no difference between the CRAI and IV groups regarding the percentages of participants who developed pancreatic necrosis (more than 1/3 of the pancreas: 25.0%, range 8.7–49.1% vs. 15.8%, range 3.4–39.6%, respectively, P = 0.694; more than 2/3 of the pancreas: 20%, range 5.7–43.7% vs. 5.3%, range 0.1–26.0%, respectively, P = 0.341). The early analgesic effect was evaluated based on 24-h cumulative fentanyl consumption and additional administration by intravenous patient-controlled analgesia. The results showed that the CRAI group used significantly less analgesic. There were two adverse events related to CRAI, namely bleeding and splenic infarction.ConclusionsCRAI with NM did not inhibit the development of pancreatic necrosis although early analgesic effect of CRAI was superior to that of IV. Less-invasive IV therapy can be considered a viable alternative to CRAI therapy.

Management of Status Epilepticus

AbstractStatus epilepticus (SE) is a life-threatening neurologic condition that requires immediate assessment and intervention. Over the past few decades, the duration of seizure required to define status epilepticus has shortened, reflecting the need to start therapy without the slightest delay. The focus of this review is on the management of convulsive and nonconvulsive status epilepticus in critically ill patients. Initial treatment of both forms of status epilepticus includes immediate assessment and stabilization, and administration of rapidly acting benzodiazepine therapy followed by nonbenzodiazepine antiepileptic drug. Refractory and super-refractory status epilepticus (RSE and SRSE) pose a lot of therapeutic problems, necessitating the administration of continuous infusion of high doses of anesthetic agents, and carry a high risk of debilitating morbidity as well as mortality.

Continuous cefazolin infusion versus cefazolin plus probenecid for the ambulatory treatment of uncomplicated cellulitis: Aretrospective cohort study.

The preferred ambulatory IV therapy for cellulitis is often once-daily cefazolin combined with once-daily oral probenecid (C+P). However, due to a national probenecid drug shortage in 2011, our centre developed a replacement protocol for the administration of cefazolin continuous infusion (CCI) using elastomeric infusers. Our goal was to compare treatment efficacy, duration of IV therapy, and recurrence associated with CCI and C+P using retrospective data from our centre. We conducted a non-inferiority single-centre retrospective cohort study of emergency department medical records. Patients received either C+P (cefazolin 2 g IV once daily plus probenecid 1 g PO once daily) or CCI (cefazolin 2 g IV loading dose, followed by cefazolin 6 g IV via continuous infusion over 24 hours, via an elastomeric infuser). We compared treatment efficacy, duration of IV therapy, and recurrence rates. total of 203 patients were analyzed, with 107 included in the CCI arm and 96 in the C+P arm. Overall, CCI users and C+P users were comparable in their sociodemographic and clinical variables measured at admission. We observed increased odds of achieving successful treatment among the CCI group, however it did not reach statistical significance (odds ratio [OR] 2.25; 95% CI 0.84 to 6.07). Recurrence rates were similar between both groups (OR 1.91; 95% CI 0.32 to 11.31). The average duration of IV therapy was similar between groups (p = 0.6). ith results suggesting that CCI was non-inferior to C+P, and that both approaches required similar treatment durations, CCI could represent an acceptable alternative to C+P for the ambulatory IV treatment of cellulitis.

Incidence of Acute Kidney Injury in Intermittent Versus Continuous Infusion of Polymyxin B in Hospitalized Patients.

Background: Studies evaluating the risk of developing acute kidney injury (AKI) with different dosing strategies of polymyxin B are limited. Objectives: To compare the incidence of AKI in patients treated with intermittent versus continuous polymyxin B therapy. Secondary objectives included time to onset of AKI, hospital length of stay (LOS), and all-cause hospital mortality. Variables associated with an increased risk of AKI were evaluated. Methods: A retrospective record review was conducted at a single center in Puerto Rico. Adult patients (≥18 years old) treated with polymyxin B (first course) for at least 48 hours from 2013-2015 were evaluated. Patients with a creatinine clearance <10 mL/min and/or on renal replacement were excluded. Results: A total of 69 patients were included: 42 in the continuous infusion and 27 in the intermittent dosing group. Incidence of AKI was not significantly different between the groups (intermittent 41% vs continuous 31%, P = 0.4). No difference was found in the onset of nephrotoxicity, hospital LOS, or all-cause hospital mortality. Variables associated with increased risk of AKI were baseline serum creatinine, age, and intensive care unit admission. Patients with a body mass index (BMI) >25 kg/m2 on polymyxin B via continuous infusion had a significantly higher cumulative incidence of AKI (P = 0.016). Conclusion and Relevance: No difference in the risk of polymyxin B nephrotoxicity was found between intermittent and continuous infusion administration. Administration of polymyxin B via a continuous infusion may result in a higher risk of AKI in patients with a BMI >25 kg/m2.

Air-in-Line Alarms: Decreasing Alarms Through Antisiphon Valve Implementation.

The administration of 24-hour continuous chemotherapy infusions is common in certain regimens, such as EPOCH (etoposide, prednisone, vincristine, cyclophosphamide, and doxorubicin). Such regimens are notorious for clinically insignificant air-in-line (AIL) alarms because of the naturally bubbly composition of the drugs involved. An antisiphon valve, placed at the end of the IV tubing to pressurize the infusion and to minimize air bubbles, was found to decrease clinically insignificant AIL alarms. The positive outcomes of the current study could be applied to other infusions known for frequent clinically insignificant AIL alarms.

PROLONGED EPIDURAL ANALGESIA AFTER COLORECTAL SURGERY IN ELDERLY PATIENTS

Objective: to compare the effectiveness of prolonged epidural analgesia by continuous infusion or bolus administration on demand, as well as the timing and volume of early mobilization with two methods of postoperative analgesia. Material and methods: prospective randomized study enrolled 161 patients with colorectal cancer aged from 60 to 89 years, operated by means of laparotomy and laparoscopy. In the main group (n=80), postoperative prolonged epidural analgesia was carried out using individual pumps with an initial rate of 0.2% ropivacaine solution of 4-6 ml/h. In the comparison group, epidural analgesia was provided by bolus administration of 4-6 ml of 0.2% ropivacaine solution on demand. Results: In the main group with open surgical interventions, in contrast to the comparison group, prolonged epidural analgesia provided a decrease in the intensity of pain on the second (2.7 ± 1.8 and 4.1 ± 1.4 score, p &lt; 0.001), third (2.6 ± 1.6 and 3.9 ± 1.1 score, p &lt; 0.001), fourth day (2.3 ± 1.7 and 3.5 ± 1.2 score, p &lt; 0.001). Prolonged epidural analgesia in the main group allowed more patients to be activated on the second (64.2% (52 of 81), p &lt; 0.001), third (97.5% (79 of 81), p &lt; 0.001) and fourth (100%, p &lt; 0.002) days. The average time of activity in the main group was three times higher on the third day and twice - on the fourth day (p &lt; 0.001). Conclusion: Postoperative prolonged epidural analgesia is highly effective in elderly patients during their treatment with enhanced recovery methods.

Factors associated with treatment delays in pediatric refractory convulsive status epilepticus.

To identify factors associated with treatment delays in pediatric patients with convulsive refractory status epilepticus (rSE). This prospective, observational study was performed from June 2011 to March 2017 on pediatric patients (1 month to 21 years of age) with rSE. We evaluated potential factors associated with increased treatment delays in a Cox proportional hazards model. We studied 219 patients (53% males) with a median (25th-75th percentiles [p25-p75]) age of 3.9 (1.2-9.5) years in whom rSE started out of hospital (141 [64.4%]) or in hospital (78 [35.6%]). The median (p25-p75) time from seizure onset to treatment was 16 (5-45) minutes to first benzodiazepine (BZD), 63 (33-146) minutes to first non-BZD antiepileptic drug (AED), and 170 (107-539) minutes to first continuous infusion. Factors associated with more delays to administration of the first BZD were intermittent rSE (hazard ratio [HR] 1.54, 95% confidence interval [CI] 1.14-2.09; p = 0.0467) and out-of-hospital rSE onset (HR 1.5, 95% CI 1.11-2.04; p = 0.0467). Factors associated with more delays to administration of the first non-BZD AED were intermittent rSE (HR 1.78, 95% CI 1.32-2.4; p = 0.001) and out-of-hospital rSE onset (HR 2.25, 95% CI 1.67-3.02; p < 0.0001). None of the studied factors were associated with a delayed administration of continuous infusion. Intermittent rSE and out-of-hospital rSE onset are independently associated with longer delays to administration of the first BZD and the first non-BZD AED in pediatric rSE. These factors identify potential targets for intervention to reduce time to treatment.

Does the Heparin Infusion Decrease the Risk of Catheter Related Thrombosis in Neonates with Central Venous Catheters?

A preterm newborn baby needs a peripherally inserted central venous catheter (PICVC) for the administration of parenteral nutrition (PN), intravenous (IV) fluids and medications. Echocardiogram is performed on this baby to ascertain the presence of PDA. Echocardiogram shows an incidental finding of inferior vena cava (IVC) thrombosis that is partially blocking the IVC. Here the question arises whether administration of continuous infusion of heparin through the central venous catheters including the umbilical venous catheters (UVC) or peripherally (percutaneous) inserted central venous catheters, commonly referred as long lines can reduce the incidence of catheter related thrombosis in neonates.

Results of two sequential phase II studies of interleukin-2 (IL2) in metastatic renal cell carcinoma and melanoma: high-dose continuous intravenous IL2 infusion and subcutaneous IL2 administration in combination with alpha interferon

The results of two sequential trials, the first one with high dose interleukin 2 (IL2) by continuous intravenous infusion and the second one with subcutaneous IL2 and alpha-interferon (alpha IFN), performed in consecutive patients with metastatic melanoma and renal carcinoma at the Clinica Universitaria de Navarra are presented. In the high-dose continuous IL2 trial, recombinant IL2, 18 x 10(6) IU/m2, was administered daily by continuous infusion five days a week for two weeks, and the treatment cycle was repeated after a rest of 2 weeks. Twenty two patients were treated and objective responses were observed in 3 (13.3%). Toxicity was frequent and severe, and all but one required dose reduction. The mortality rate was 9% (2/22). In the subcutaneous IL2 and alpha IFN trial, subcutaneous IL2, 4.8 x 10(6) IU/m2, was administered daily, five days a week, for 3 consecutive weeks. IL2 dose was given every 8 hours on the first day and every 12 hours on the second day, as a loading induction dose. Concomitant alpha-IFN, 3 x 10(6) IU/m2 was given subcutaneously once a day on days 1, 3 and 5 weekly each week for the duration of IL2 therapy. Of the 24 patients treated with this combination, 3 partial responses were noticed (12.5%) and the toxicity was mild to moderate. These results suggest that both, IL2 alone or IL2 in combination with alpha-IFN are minimally active and that any improvement in tolerance might impair its antitumor activity.