Does carrier fluid reduce low flow drug infusion error from syringe size?

BACKGROUND: Critically ill neonates and pediatric patients commonly require multiple low flow infusions. Volume limitations are imposed by small body habitus and co-morbidities like cardiopulmonary disease, renal failure, or fluid overload. Vascular access is limited by diminutive veins. Maintenance fluids or parenteral nutrition in conjunction with actively titrated infusions such as insulin, fentanyl, prostaglandins, inotropes and vasopressors may necessitate simultaneous infusions using a single lumen to maintain vascular catheter patency. This requirement for multiple titratable infusions requires concentrated medications at low flows, rather than more dilute drugs at higher flows that in combination may volume overload small infants. AIM: To determine whether carrier fluid reduces variability that variability of low flow drug infusions is proportional to syringe size in pediatric critical care. METHODS: We assessed concentrations of orange "drug" in a 0.2 mL/h low flow clinical model with blue dyed carrier fluid at 5 mL/h, using 3-, 10-, or 60-mL syringes. A graduated volumetric pipette was used to measure total flow. Mean time to target concentration was 30, 21, and 46 min in 3-, 10-, and 60-mL syringes, respectively (P = 0.42). After achieving target concentration, more dilute drug was delivered by 60-mL (P < 0.001) and 10-mL syringes (P = 0.04) compared to 3-mL syringes. Drug overdoses were observed during the initial 45 min of infusion in 10-and 60-mL syringes. Total volumes infused after target concentration were less in the 60-mL condition compared to 3-mL (P < 0.01) and 10-mL (P < 0.001) syringes. RESULTS: Linear mixed effects models demonstrated lesser delivered drug concentrations in the initial 30 min by 3-mL compared to 10-and 60-mL syringes (P = 0.005 and P < 0.001, respectively) but greater drug concentrations and total infused drug in the subsequent 30-60 and 60-90 min intervals with the 3- and 10-mL compared to 60-mL syringes. CONCLUSION: With carrier fluid, larger syringes were associated with significantly less drug delivery, less total volume delivered, and other flow problems in our low flow drug model. Carrier fluid should not be used to compensate for inappropriately large syringes in critical low flow drug infusions.

Ethics of organ procurement from the unrepresented patient population.

The shortage of organs for transplantation by its nature prompts ethical dilemmas. For example, although there is an imperative to save human life and reduce suffering by maximising the supply of vital organs, there is an equally important obligation to ensure that the process by which we increase the supply respects the rights of all stakeholders. In a relatively unexamined practice in the USA, organs are procured from unrepresented decedents without their express consent. Unrepresented decedents have no known healthcare wishes or advance care planning document; they also lack a surrogate. The Revised Uniform Anatomical Gift Act (RUAGA) of 2006 sends a mixed message about the procurement of organs from this patient population and there are hospitals that authorise donation. In addition, in adopting the RUAGA, some states included provisions that clearly allow organ procurement from unrepresented decedents. An important unanswered question is whether this practice meets the canons of ethical permissibility. The current Brief Report presents two principled approaches to the topic as a way of highlighting some of the complexities involved. Concluding remarks offer suggestions for future research and discussion.

Pain Sensitization, Breastfeeding Effectiveness, and Parental Preferences by Antibiotic Route in Suspected Neonatal Sepsis.

OBJECTIVES: Intravenous (IV) and intramuscular (IM) antibiotics have comparable efficacy in treating neonates undergoing sepsis evaluations. There are no clinical data favoring the use of either route regarding newborn pain and parental preferences. We hypothesized that pain associated with IM injections would worsen breastfeeding effectiveness and decrease parental satisfaction, making IV catheters the preferred route. METHODS: This prospective cohort study took place in an academic institution with nurseries in 2 separate hospitals, 1 providing IV antibiotics, and the other, IM antibiotics. Newborns receiving 48 hours of antibiotics were compared by using objective pain and breastfeeding scores and parental surveys. RESULTS: In 185 newborns studied, pain scores on a 7-point scale were up to 3.4 points higher in the IM compared with the IV group (P < .001). Slopes of repeated pain scores were 0.42 ± 0.08 and -0.01 ± 0.11 in the IM and IV groups, respectively (P = .002). Breastfeeding scores were similar between groups. Parents in the IV group were less likely to perceive discomfort with antibiotic administration (odds ratio [OR] 0.22; 95% confidence interval [CI] 0.06-0.74) but more likely to perceive interference with breastfeeding (OR 26; 95% CI 6.4-108) and bonding (OR 101; 95% CI 17-590) and more likely to prefer changing to the alternate route (OR 6.9; 95% CI 2.3-20). CONCLUSIONS: IM antibiotics in newborns are associated with pain sensitization and greater pain than IV dosing. Despite accurately recognizing newborn pain with the IM route, parents preferred this to the IV route, which was perceived to interfere with breastfeeding and bonding.

Clinical characteristics and outcomes associated with nasal intermittent mandatory ventilation in acute pediatric respiratory failure.

AIM: To characterize the clinical course and outcomes of nasal intermittent mandatory ventilation (NIMV) use in acute pediatric respiratory failure. METHODS: We identified all patients treated with NIMV in the pediatric intensive care unit (PICU) or inpatient general pediatrics between January 2013 and December 2015 at two academic centers. Patients who utilized NIMV with other modes of noninvasive ventilation during the same admission were included. Data included demographics, vital signs on admission and prior to initiation of NIMV, pediatric risk of mortality III (PRISM-III) scores, complications, respiratory support characteristics, PICU and hospital length of stays, duration of respiratory support, and complications. Patients who did not require escalation to mechanical ventilation were defined as NIMV responders; those who required escalation to mechanical ventilation (MV) were defined as NIMV non-responders. NIMV responders were compared to NIMV non-responders. RESULTS: Forty-two patients met study criteria. Six (14%) failed treatment and required MV. The majority of the patients (74%) had a primary diagnosis of bronchiolitis. The median age of these 42 patients was 4 mo (range 0.5-28.1 mo, IQR 7, P = 0.69). No significant difference was measured in other baseline demographics and vitals on initiation of NIMV; these included age, temperature, respiratory rate, O2 saturation, heart rate, systolic blood pressure, diastolic blood pressure, and PRISM-III scores. The duration of NIMV was shorter in the NIMV non-responder vs NIMV responder group (6.5 h vs 65 h, P < 0.0005). Otherwise, NIMV failure was not associated with significant differences in PICU length of stay (LOS), hospital LOS, or total duration of respiratory support. No patients had aspiration pneumonia, pneumothorax, or skin breakdown. CONCLUSION: Most of our patients responded to NIMV. NIMV failure is not associated with differences in hospital LOS, PICU LOS, or duration of respiratory support.

Attenuation of Oxidative Stress-Induced Cell Apoptosis in Schwann RSC96 Cells by Ocimum Gratissimum Aqueous Extract.

Objectives: Cell transplantation therapy of Schwann cells (SCs) is a promising therapeutic strategy after spinal cord injury. However, challenges such as oxidative stress hinder satisfactory cell viability and intervention for enhancing SCs survival is critical throughout the transplantation procedures. Ocimum gratissimum, widely used as a folk medicine in many countries, has therapeutic and anti-oxidative properties and may protect SCs survival. Methods: We examined the protective effects of aqueous O. gratissimum extract (OGE) against cell damage caused by H2O2-induced oxidative stress in RSC96 Schwann cells. Results: Our results showed that the RSC96 cells, damaged by H2O2 oxidative stress, decreased their viability up to 32% after treatment with different concentrations of up to 300 µM H2O2, but OGE pretreatment (150 or 200 µg/mL) increased cell viability by approximately 62% or 66%, respectively. Cell cycle analysis indicated a high (43%) sub-G1 cell population in the H2O2-treated RSC96 cells compared with untreated cells (1%); whereas OGE pretreatment (150 and 200 µg/mL) of RSC96 cells significantly reduced the sub-G1 cells (7% and 8%, respectively). Furthermore, Western blot analysis revealed that OGE pretreatment inhibited H2O2-induced apoptotic protein caspase-3 activation and PARP cleavage, as well as it reversed Bax up-regulation and Bcl-2 down-regulation. The amelioration of OGE of cell stress and stress-induced apoptosis was proved by the HSP70 and HSP72 decrease. Conclusion: Our data suggest that OGE may minimize the cytotoxic effects of H2O2-induced SCs apoptosis by modulating the apoptotic pathway and could potentially supplement cell transplantation therapy.

Ocimum gratissmum aqueous extract reduces plasma lipid in hypercholesterol-fed hamsters.

Objectives: Hyperlipidemia is a significant risk factor in the development of atherosclerosis and related diseases which are major health problem in many developed and developing countries that can lead to fatality due to the changes in lifestyle and dietary habits in this modern age. Methods: In the present study, the Ocimum gratissimum aqueous extract (OGE) was tested for the lowering effect on the serum lipid level of male hamsters on a high-fat (12%) and high-cholesterol (0.2%) diet (HFCD). Results: The results showed that the levels of serum high-density-lipoprotein-cholesterol (HDL-C) low-density-lipoprotein-cholesterol (LDL-C), total cholesterol (TC), and triglycerols (TG) were increased in the HFCD group (113±11, 259±87, 629±175 and 625±262, respectively), as compared to the control normal diet group (51±8, 19±5, 77±16 and 101±44, respectively). When co-treated with various doses (10 and 20 mg/kg) of the OGE or rosuvastatin, the rats exhibited the restoration of normal serum LDL-C, TC, and TG levels. Conclusion: Therefore, we suggest that the Ocimum gratissimum aqueous extract may have the potential function of lowering serum lipid in rats.

From bronchiolitis guideline to practice: A critical care perspective.

Acute viral bronchiolitis is a leading cause of admission to pediatric intensive care units, but research on the care of these critically ill infants has been limited. Pathology of viral bronchiolitis revealed respiratory obstruction due to intraluminal debris and edema of the airways and vasculature. This and clinical evidence suggest that airway clearance interventions such as hypertonic saline nebulizers and pulmonary toilet devices may be of benefit, particularly in situations of atelectasis associated with bronchiolitis. Research to distinguish an underlying asthma predisposition in wheezing infants with viral bronchiolitis may one day lead to guidance on when to trial bronchodilator therapy. Considering the paucity of critical care research in pediatric viral bronchiolitis, intensive care practitioners must substantially rely on individualization of therapies based on bedside clinical assessments. However, with the introduction of new diagnostic and respiratory technologies, our ability to support critically ill infants with acute viral bronchiolitis will continue to advance.

The use of renal replacement therapy in critically ill pediatric small bowel transplantation candidates and recipients: Experience from one center.

Outcomes for pediatric SBT patients requiring perioperative RRT in the PICU remain unknown. The objectives were to document our center's experience with PICU SBT patients receiving perioperative RRT and to identify variables predictive of survival to discharge. A retrospective chart review of patients (ages, 0-18 yr) between January 1, 2000 and December 31, 2011 that received RRT within a SBT perioperative period and were transplanted at our university-affiliated, tertiary care children's hospital was performed. Six SBT patients received perioperative RRT (ages, 5-12 yr). Three patients (50%) survived to hospital discharge. Among survivors, RRT was required for a total of 1-112 days (mean, 49.7 days). All three survivors survived to hospital discharge without renal transplantation and free of RRT. There was a trend toward increased survival among older patients receiving RRT (p = 0.05). Survivors had a higher I-125 GFR prior to PICU admission (p = 0.045). A higher I-125 GFR prior to PICU admission among survivors may support this test's utility during SBT evaluation. In our experience, a high survival rate and freedom from RRT at the time of discharge support RRT use in the SBT population.

Cardiac hypertrophy-related pathways in obesity.

Obesity is often associated with the development of cardiac hypertrophy but the hypertrophy-related pathways in obesity remain unknown. The purpose of this study was to evaluate cardiac hypertrophy-related markers, atrial natriuretic peptide (ANP), B-type natriuretic peptide (BNP), tumor necrosis factor-alpha (TNFα) and hypertrophy-related pathways, interleukin (IL)-6-STAT3, IL-6-MEK5-ERK5 and calcineurin-nuclear factor of activated T-cells (NFAT)3 in the excised hearts from obese rats. Twelve obese Zucker rats were studied at 5-6 months of age and twelve age-matched lean Zucker rats served as the control group. The cardiac characteristics, myocardial architecture, ANP, BNP, TNFα levels, IL-6, STAT3, p-STAT3, MEK5, ERK-5, p-ERK-5, calcineurin and NFAT3 in the left ventricle from the rats were measured by heart weight index, echocardiography, vertical cross section, histological analysis, reverse transcription polymerase chain reaction and western blotting. Compared with the lean control, the whole heart weight, the left ventricule weight, the ratio of the whole heart weight to tibia length, echocardiographic interventricular septum, left ventricular posterior wall thickness, myocardial morphological changes and systolic blood pressure were found to increase in the obese rats. The protein levels of ANP, BNP, TNFα, IL-6, STAT3, p-STAT3, MEK-5, ERK-5, p-ERK 5, calcineurin and NFAT3 were also significantly increased in the hearts of the obese rats. The results showed that the hypertrophy-related markers, ANP, BNP and TNFα, the hypertrophy-related pathways IL-6-STAT3 and IL-6-MEK5-ERK5, and the calcineurin-NFAT3 hypertrophy-related pathways were more active in obese Zucker rats, which may provide possible hypertrophic mechanisms for developing cardiac hypertrophy and pathological changes in obesity.

The Management of Spontaneous Otogenic CSF Leaks: A Presentation of Cases and Review of Literature.

Objective The types of otogenic cerebrospinal fluid (CSF) fistulae were previously classified into defects through, adjacent to, or distal to the otic capsule. This article presents cases of the three different types of spontaneous CSF fistulae and reviews pertinent literature. We examine the management of the different types of otogenic CSF leaks with modern audiovestibular testing, imaging, and surgical techniques. Design Case series and review of the literature. Setting Academic tertiary neurotologic referral practice. Participants Four patients identified through a retrospective search. Main outcome measures Resolution of CSF leak and absence of meningitis. Results Surgical intervention was performed on the four cases described in this series; none had a return of CSF otorrhea in the postoperative period or meningitis. Conclusions Otogenic CSF fistulae may lead to life-threatening infection and in congenital forms are typically not diagnosed unless meningitis has occurred. Rapid and proper recognition, work-up, and treatment of such leaks decrease the risk of permanent neurologic sequelae as well as recurrent meningitis.

Herbal supplement attenuation of cardiac fibrosis in rats with CCl4-induced liver cirrhosis.

Previously we found carbon tetrachloride (CCl4) induced cirrhosis associated cardiac hypertrophy and apoptosis. The purpose of this study is to determine whether further CCl4 treatment would induce cardiac cell fibrosis. The cardiac tissues were analyzed by H&E. histological staining, Trichrome Masson staining and Western blotting. The results showed that the CCl4-treated-only group exhibits more trichrome staining, meaning that more fibrosis is present. Moreover, CCl4 could further induce cardiac-fibrosis via TGF-ß-p-Smad2/3-CTGF pathway. However, our data showed that the CCl4- indcued cardiac abnormalities were attenuated by Ocimum gratissimum extract (OGE) and silymarin co- treatments. In conclusion, our results indicated that the OGE and silymarin may be a potential traditional herb for the protection of cardiac tissues from the CCl4 induced cirrhosis associated cardiac fibrosis through modulating the TGF-ß signaling pathway.

Endothelin-1 enhances cell migration through COX-2 up-regulation in human chondrosarcoma.

BACKGROUND: Chondrosarcoma is a type of highly malignant tumor with a potent capacity of local invasion and distant metastasis. The effect of endothelin-1 (ET-1) on migration activity in human chondrosarcoma cells is not clearly understood. Here, we found that ET-1 increased the migration and expression of cyclooxygenase (COX)-2 in human chondrosarcoma cells. METHODS: ET-1-mediated COX-2 expression was assessed by qPCR and Western blot analysis. The mechanisms of action of ET-1 in different signaling pathways were studied using Western blotting. Knockdown of proteins was achieved by transfection with siRNA. Chromatin immunoprecipitation assays were used to study in vivo binding of c-Jun to the COX-2 promoter. RESULTS: Human chondrosarcoma tissues had significant expression levels of ET-1 and COX-2, which were higher than that in normal cartilage. Exogenous ET-1 increased cell migration and the expression of COX-2. In addition, COX-2 protein levels and cell migration ability were abolished by ET receptor antagonists. Activation of the mitogen-activated protein kinase (MAPK) and activator protein-1 (AP-1) pathways after ET-1 treatment was demonstrated, and ET-1-induced COX-2 expression and cell migration activity were inhibited by the specific inhibitor and mutant of MAPK and AP-1 cascades. ET-1 increased the binding of c-Jun to the AP-1 element on the COX-2 promoter. Furthermore, knockdown of ET-1 decreased cell metastasis in vitro and in vivo. CONCLUSIONS: Our results indicated that ET-1 enhances the cell migration of chondrosarcoma by increasing COX-2 expression through the ET receptors, MAPK, and AP-1 signal transduction pathway. GENERAL SIGNIFICANCE: We link high ET-1 and COX-2 expression to chondrosarcoma.

Danshen mediates through estrogen receptors to activate Akt and inhibit apoptosis effect of Leu27IGF-II-induced IGF-II receptor signaling activation in cardiomyoblasts.

Post-menopausal women show dramatically increased cardiovascular disease morbidity (CVD). Danshen is used widely in China for the treatment of cardiovascular disorders, including coronary heart disease. Danshen possesses lipid-soluble biologically active components with a structure similar to 17ß-estrodiol (E2). This study assesses whether the cardio-protection exerted by Danshen is mediated through the ERs within H9c2 cardiomyoblast cells. Cardiomyoblast cells pretreated with Fulvestrant (ICI 182,780), an estrogen receptor antagonist was applied to investigate the estrogenic activity of Danshen. The Danshen extract preventive effects on Leu27IGF-II-induced IGF-IIR signaling activator and H9c2 cell apoptosis were identified using TUNEL assay, JC-1 staining and Western blot assay. We found that Danshen extract treatments significantly enhanced phosphorylated Akt through estrogen receptor activation to inhibit Leu27IGF-II-induced calcineurin activation and block H9c2 cell apoptosis. Danshen extracts suppressed the IGF-IIR signaling proteins, pro-apoptotic proteins and reversed the mitochondrial membrane instability induced by Leu27IGF-II. However, the cardioprotective properties of Danshen to inhibit Leu27IGF-II-induced cell apoptosis and promote cell survival were attenuated by applying ICI, which suggests that the Danshen cardioprotective effect is mediated through estrogen receptors. All our data indicated that Danshen exerts strong estrogenic activity which can be considered a novel selective estrogen receptor modulator (SERM) against IGF2R signaling that blocks cardiac apoptosis.

Exercise training enhances cardiac IGFI-R/PI3K/Akt and Bcl-2 family associated pro-survival pathways in streptozotocin-induced diabetic rats.

BACKGROUND: Increased myocyte apoptosis in diabetic hearts has been previously reported. The purpose of this study was to evaluate the effects of exercise training on cardiac survival pathways in streptozotocin (STZ)-induced diabetic rats. METHODS: Forty-eight male Wistar rats were randomly divided into control group (Control), STZ-induced (65 mg/kg, i.p.) diabetes (DM), and DM rats with moderate aerobic exercise training (DM-EX) on a treadmill 60 min/day, 5 days/week, for 10 weeks. Histopathological analysis, positive TUNEL assays and Western blotting were performed on the excised cardiac left ventricles from all three groups. RESULTS: The components of cardiac survival pathway (insulin-like growth factor I (IGFI), IGFI-receptor (IGFI-R), phosphatidylinositol 3'-kinase (PI3K), and Akt) and the pro-survival Bcl-2 family proteins (Bcl-2, Bcl-xL, and p-BAD) were all significantly decreased in the DM group compared with the Control group whereas they were increased in the DM-EX group. In addition, the abnormal myocardial architecture, enlarged interstitial space and increased cardiac TUNEL-positive apoptotic cells were observed in the DM group, but they were reduced in the DM-EX group. The apoptotic key component, caspase-3, was significantly increased in the DM group relative to the Control group whereas it was decreased in the DM-EX group. CONCLUSIONS: Exercise training enhances cardiac IGFI-R/PI3K/Akt and Bcl-2 family associated pro-survival pathways, which provides one of the new beneficial effects for exercise training in diabetes.

Garlic oil attenuates the cardiac apoptosis in hamster-fed with hypercholesterol diet.

Hypercholesterolemia is a well established risk factor for cardiac cell apoptosis. The purpose of this study is to evaluate the effects of garlic oil on cardiac apoptosis induced by a hypercholesterol diet. Twenty-four male Golden-Syrian hamsters at 3 months of age were randomly divided into three groups, control, cholesterol and garlic oil groups received a chow diet, chow diet with 2% cholesterol, and chow diet with 2% cholesterol and 1% garlic oil for 8 weeks, respectively. The TUNEL-positive apoptotic cells, and several apoptotic proteins were significantly induced in the excised left ventricle in cholesterol group, whereas significant reduction was observed in cholesterol plus garlic oil group. The IGFI receptor dependent survival pathway was inhibited in cholesterol group whereas it was obviously reversed in cholesterol plus garlic oil group. Our results suggest that administration of garlic oil shows protective effects on cardiac apoptosis in rats with high cholesterol intake.