Average Infusion Rate Research Articles

Dissecting genetic factors affecting phenylephrine infusion rates during anesthesia: a genome-wide association study employing EHR data

BackgroundThe alpha-adrenergic agonist phenylephrine is often used to treat hypotension during anesthesia. In clinical situations, low blood pressure may require prompt intervention by intravenous bolus or infusion. Differences in responsiveness to phenylephrine treatment are commonly observed in clinical practice. Candidate gene studies indicate genetic variants may contribute to this variable response.MethodsPharmacological and physiological data were retrospectively extracted from routine clinical anesthetic records. Response to phenylephrine boluses could not be reliably assessed, so infusion rates were used for analysis. Unsupervised k-means clustering was conducted on clean data containing 4130 patients based on phenylephrine infusion rate and blood pressure parameters, to identify potential phenotypic subtypes. Genome-wide association studies (GWAS) were performed against average infusion rates in two cohorts: phase I (n = 1205) and phase II (n = 329). Top genetic variants identified from the meta-analysis were further examined to see if they could differentiate subgroups identified by k-means clustering.ResultsThree subgroups of patients with different response to phenylephrine were clustered and characterized: resistant (high infusion rate yet low mean systolic blood pressure (SBP)), intermediate (low infusion rate and low SBP), and sensitive (low infusion rate with high SBP). Differences among clusters were tabulated to assess for possible confounding influences. Comorbidity hierarchical clustering showed the resistant group had a higher prevalence of confounding factors than the intermediate and sensitive groups although overall prevalence is below 6%. Three loci with P < 1 × 10−6 were associated with phenylephrine infusion rate. Only rs11572377 with P = 6.09 × 10−7, a 3′UTR variant of EDN2, encoding a secretory vasoconstricting peptide, could significantly differentiate resistant from sensitive groups (P = 0.015 and 0.018 for phase I and phase II) or resistant from pooled sensitive and intermediate groups (P = 0.047 and 0.018).ConclusionsRetrospective analysis of electronic anesthetic records data coupled with the genetic data identified genetic variants contributing to variable sensitivity to phenylephrine infusion during anesthesia. Although the identified top gene, EDN2, has robust biological relevance to vasoconstriction by binding to endothelin type A (ETA) receptors on arterial smooth muscle cells, further functional as well as replication studies are necessary to confirm this association.

PSY140 - DEXMEDETOMIDINE UTILISATION STUDY IN THE INTENSIVE CARE UNIT

To describe the patterns of dexmedetomidine use in the Intensive Care Unit (ICU) in a tertiary hospital and the impact of pharmacy intervention on it. Prospective four-month study (October 2017-January 2018). There was a greater use of dexmedetomidine in November so pharmacists encouraged physicians to consider protocols before prescribing. Dexmedetomidine 1mg/10 ml vial is administered as a solution (4 mcg/ml) by intravenous perfusion at dose range: 0.2-1.4 mcg/kg/hour. Data collected: treatment days with dexmedetomidine or sedative drugs combination, oral clonidine consumption, dexmedetomidine solution used (ml/day), infusion rates used (milliliters/h), RASS level and vials dispensed/month. Thirty-one patients received dexmedetomidine. Median duration of treatment was 1.8 days(maximum 8 days). Two patients(6.5%) received the combination formed by Remifentanil+Propofol+Midazolam+Dexmedetomidine, although it was less than 24 hours. Average dexmedetomidine solution administered/patient: 175 ml/day(48-672); average dexmedetomidine infusion rate: 9.9 ml/h(2-28). RASS level was not recorded any time during dexmedetomidine treatment in 13 patients (41.9%). Seven patients(22.6%) registered a RASS value lower than -3, two of them received treatment with dexmedetomidine during 6 and 7 days of respectively. Dexmedetomidine consumption in ICU was 26, 114, 91 and 76 vials for each month of this study. In three patients(9.7%) dexmedetomidine was replaced by clonidine when possible (clonidine was not prescribed in the first two months; in December and in January it was dispensed 91 and 48 tablets respectively). During the study, two cases of incorrect use were detected(6.5%). Dexmedetomidine consumption has been clearly reduced since the intervention halfway through the study period, and the use of clonidine was favored in its place. In most cases the use of dexmedetomidine was indicated and correctly justified. The importance in these cases lies in the need to establish maximum times from which the combination of dexmedetomidine should not be overcome with several sedatives for own use in deep sedation levels.

Hydrochloric Acid Infusion for the Treatment of Metabolic Alkalosis in Surgical Intensive Care Unit Patients.

Older reports of use of hydrochloric acid (HCl) infusions for treatment of metabolic alkalosis document variable dosing strategies and risk. This study sought to characterize use of HCl infusions in surgical intensive care unit patients for the treatment of metabolic alkalosis. This retrospective review included patients who received a HCl infusion for >8 hours. The primary end point was to evaluate the utility of common acid-base equations for predicting HCl dose requirements. Secondary end points evaluated adverse effects, efficacy, duration of therapy, and total HCl dose needed to correct metabolic alkalosis. Data on demographics, potential causes of metabolic alkalosis, fluid volume, and duration of diuretics as well as laboratory data were collected. A total of 30 patients were included, and the average HCl infusion rate was 10.5 ± 3.7 mEq/h for an average of 29 ± 14.6 hours. Metabolic alkalosis was primarily diuretic-induced (n = 26). Efficacy was characterized by reduction in the median total serum CO2 from 34 to 27 mM/L ( P < 0.001). The change in chloride ion deficit and change in apparent strong ion difference (SIDa) were not correlated with total HCl administered. There were no documented serious adverse effects related to HCl infusions. HCl was effective for treating metabolic alkalosis, and no serious adverse events were seen. In this clinical setting, the baseline chloride ion deficit and SIDa were not useful for prediction of total HCl dose requirement, and serial monitoring of response is recommended.

831: The effect of an oxytocin checklist for EMR clinical decision support in labor on oxytocin use and maternal/neonatal outcomes in a clinical practice setting

Oxytocin is associated with preventable adverse events during labor. Oxytocin dosing is complex due to a wide therapeutic index and lack of consensus on optimal dosing and regimen. In 2013, the Perinatal Patient Safety group within Kaiser Permanente Northern California created an oxytocin checklist to reduce and standardize dosing, first on paper then as a clinical decision support tool in the electronic medical record (EMR). We sought to assess the effect of the checklist on oxytocin usage and clinical outcomes over time. We performed a retrospective cohort study from October 2012 to December 2016 of 34,612 singleton gestations at 37w0d or greater who received oxytocin in labor. We compared oxytocin use (initial and highest infusion rates, average infusion rate, duration of use) and labor outcomes (admission to delivery time, operative delivery rate), for 3 groups: 1) pre-checklist implementation; 2) after paper checklist implementation; and 3) after implementation of EMR clinical decision support. We also examined infant outcomes (NICU admission, 5-minute Apgar <7, mechanical ventilation) and stratified by mode of delivery. Compared to pre-checklist, the paper checklist and decision support groups had a lower average and cumulative infusion rate, lower highest infusion rate, and longer duration of oxytocin use (Table). The change was greatest in the decision support group. The time from admission to delivery increased by 3.6 hours for the decision support compared to the pre-checklist groups. When stratifying by mode of delivery, findings were similar. The greatest change was seen in the cesarean delivery group, with a mean reduction of 760 mU of oxytocin and an increase of 4.7 hours between pre-checklist and decision support groups. The cesarean section rate and 5-minute Apgar <7, infant intubation, and infant length of stay were unchanged. Compared to pre-checklist, the decision support group was associated with a decrease in NICU admissions and in infants requiring oxygen after birth. Use of EMR clinical decision support with an oxytocin checklist is associated with improved clinical practice patterns and neonatal outcomes, at the expense of longer labor times.

PP-41 Risk assessment for compatibility of rhigf-1/rhigfbp-3 with commonly administered neonatal intravenous medications based on an experimental model

Background Despite extensive co-administration of drugs to neonates, drug-drug compatibility has not gen-erally been tested before medicines are introduced to this population. Recombinant human (rh)IGF-1/IGFBP-3 (a protein complex) is being studied for the prevention of complications of prematurity, administered as a continuous intravenous (IV) infusion in preterm infants. Due to limited line access in neonates, coadministration with other medications via a terminal injection site would be desirable for use in clinical practice. A comprehensive risk assessment based on in vitro testing is evaluating the physical/chemical compatibility of rhIGF-1/IGFBP-3 with medications routinely administered intravenously in the neonatal intensive care unit (NICU). We report initial re-sults from the panel of medications assessed to date. Methods Medications most likely to be co-infused with rhIGF-1/IGFBP-3 were identified at the start of the risk as-sessment by consulting sites for a clinical trial. In vitro mix-ing of rhIGF-1/IGFBP-3 with each test medication (pre-dominantly small molecules) was performed based on different volumes and/or mass ratios to mimic different dose ranges. Duration of mixing was based on average infusion rates of rhIGF-1/IGFBP-3 with each test medica-tion at the highest dose, and an estimated volume for an umbilical catheter. Physical compatibility was assessed by visual observation, optical density at 320 nm, pH, and os-molality for each mixed solution and compared with the corresponding controls. Where there was no observed colour change, precipitation, turbidity, gas evolution or clinically relevant change in pH or osmolality, the mix-tures were considered compatible. The concentration of each test medication post-mixing was assessed using re-versed phase high performance liquid chromatography. A comprehensive risk evaluation was conducted for each medication based on the in vitro physical/chemical com-patibility data, theoretical potential for chemical modifi-cation, and clinical co-infusion history/experiences. Results In vitro studies and risk evaluations have been completed for rhIGF-1/IGFBP-3 with 13 medications: do-pamine, parenteral nutrition (PN), PN+Intralipid 20%, Intr-alipid 20%, dobutamine, vancomycin, morphine, fentanyl, midazolam, fluconazole, caffeine citrate, amikacin and in-sulin. In vitro physical compatibility was established with 10/13 medications: parenteral nutrition (PN), PN+Intralip-id 20%, Intralipid 20%, dobutamine, vancomycin, mor-phine, fentanyl, midazolam, fluconazole and insulin. Phys-ical compatibility was not established with 3/13 medica-tions: dopamine, caffeine citrate and amikacin, owing to changes in pH post-mixing. Small molecule content was not affected post-mixing for the medications tested. A comprehensive risk evaluation confirmed a low risk for the probability/severity of a ‘risk event’ (defined as in-compatibility with the co-infused drug over the duration and condition of the simulated mixing studies) for those medications showing in vitro compatibility. Conclusion Case-by-case, in vitro compatibility data for rhIGF-1/rhIGFBP-3 to date have been encouraging and indicate the likelihood of being able to co-infuse rhIGF-1/rhIGFBP-3 with the tested medicines. Further work is on-going to systematically evaluate compatibility with other IV drugs used in the NICU and develop protein-specific assays to test chemical compatibility of rhIGF-1/IGFBP-3. We believe this work will establish a new benchmark for compatibility testing of drugs utilised in neonates; con-tributions from clinicians and cross-functional disciplines will be key to the process.

The impact of kidney transplantation on insulin sensitivity.

To investigate the impact of kidney transplantation (KTx) on insulin sensitivity affecting glucose metabolism. 9 nondiabetic patients awaiting living donor KTx were examined prior to transplantation with an oral glucose tolerance test and a 3-h hyperinsulinaemic-euglycaemic clamp. The clamp was repeated 6 months after KTx. Nine age-, gender- and body mass index (BMI)-matched individuals with normal kidney function served as controls. Endogenous glucose production and glucose disappearance rate (N = 6) were measured in a subgroup of patients with corresponding controls. Results presented as mean [range]. Two patients had pretransplant prediabetes, whereas all others had normal glucose tolerance. After KTx, average glucose infusion rate to maintain euglycaemia during clamp declined significantly from 15.1 [9.1-23.7] to 9.8 [2.8-14.6] μmol/kg/min (P < 0.01) with 20.2 [9.9-33.7] μmol/kg/min in controls. Endogenous glucose production increased from 7.0 [4.8-8.5] to 9.4 [7.4-11.8] μmol/kg/min (P < 0.05) with 7.0 [-3.8 to 10.1] μmol/kg/min in controls. Glucose disappearance rate was unchanged (18.1 [12.9-24.5] vs. 17.1 [12.2-22.7] μmol/kg/min, NS) with 22.3 [14.6-34.3] in controls. In conclusion, insulin sensitivity is reduced 6 months after KTx and characterized mainly by impaired suppression of the endogenous glucose production.

Elevation of blood β-hydroxybutyrate concentration affects glucose metabolism in dairy cows before and after parturition

Recent studies in mid- and late-lactation dairy cows showed that β-hydroxybutyrate (BHB) infusion had a considerable effect on glucose metabolism and immune response during intramammary lipopolysaccharide challenge. The objective of the present study was to infuse BHB during the dry period and after parturition to investigate the effects of elevated plasma BHB concentrations on metabolism and endocrine changes in transition dairy cows. The hypothesis tested was that regulation of glucose metabolism would change at different physiological stages and an additional elevation of BHB concentration would alter glucose concentration. Multiparous Holstein cows in wk -2 (antepartum, a.p.; n = 6) and wk +2 (postpartum, p.p.; n = 8) relative to calving were infused (4 h from 0800 to 1200 h) with a BHB solution to increase plasma BHB concentration to 1.5 to 2.0 mmol/L (HyperB). The same period the next day without any infusion was considered the control period (CON). Blood samples were taken 1 h before the start of infusion as reference samples and every 30 min during the following 6 h (4 h of infusion and 2 h after infusion) in the HyperB and CON periods, and analyzed for glucose, BHB, insulin, and glucagon concentrations. During the steady state period (the latter 2 h of the 4-h infusion), plasma BHB concentration reached 1.87 ± 0.05 mmol/L (a.p.) and 1.93 ± 0.05 mmol/L (p.p.) in HyperB compared with 0.55 ± 0.06 mmol/L (a.p.) and 0.64 ± 0.04 mmol/L (p.p.) in CON, respectively. The 4-h average BHB infusion rate was 12.4 ± 1.0 and 13.3 ± 0.9 μmol/kg of BW per minute in wk -2 and +2, respectively. Infusion of BHB caused a decrease of plasma glucose concentrations relative to preinfusion levels both before and after parturition, although basal glucose concentrations were different before and after calving. Infusion of BHB increased plasma insulin concentrations a.p. but not p.p., despite a higher basal insulin concentration before than after parturition. These findings show that effects of hyperketonemia on plasma glucose concentrations are similar before and after calving but that endocrine adaptation to hyperketonemia differs before and after parturition. We assume that BHB is a metabolic key regulator in early lactating dairy cows and may affect glucose concentration by further pathways such as gluconeogenesis and altered lipolysis.

Comparative Evaluation of Ropivacaine and Fentanyl Versus Ropivacaine and Fentanyl with Clonidine for Postoperative Epidural Analgesia in Total Knee Replacement Surgery.

Clonidine an alpha 2 adrenoceptor agonist possesses analgesic properties and has been used as an adjuvant in epidural analgesia. The addition of clonidine to other analgesics may result in enhanced analgesia through additive mechanisms or synergistic mechanisms. The enhanced analgesia may lead to a decrease in the dosage of analgesic drugs along with reduction of side effects. The purpose of this study was to evaluate the effect of adding clonidine to epidural ropivacaine and fentanyl mixture in terms of quality of analgesia and side effects in patients of total knee replacement surgery. A prospective randomised double blind study was conducted on 60 patients of ASA physical status I, II and III who underwent unilateral total knee replacement surgery under combined spinal epidural anaesthesia. Patients were divided into two Groups A and B randomly. Postoperatively Group A received continuous epidural infusion of ropivacaine 2 mg.ml -1 and fentanyl 2 μg.ml -1 along with clonidine 2 μg.ml-1 in the range of 3-7 ml.hr-1 while Group B received the ropivacaine and fentanyl epidural solution. The postoperative VAS scores, haemodynamic parameters, motor block, sedation, nausea, vomiting and any other significant side effects were noted. The two groups were compared with student's t-test, Pearson's Chi square test and t-test using SPSS statistical software. Visual analog scale scores were lower in Group A (3.38) than in Group B (3.72). The average infusion rate was lower in Group A (4.7 ± 0.7 ml.hr -1) than in Group B (5.5 ± 0.7 ml.hr-1). Patients in Group A required less dosage of rescue pain medication Paracetamol (1g i.v.), diastolic pressure and heart rate were lower in Group A. The groups were comparable in terms of sedation, motor block and nausea vomiting. Clonidine added to a ropivacaine and fentanyl mixture augmented the postoperative epidural analgesia without significant side effects.

Intravenous ketamine for subacute treatment of refractory chronic migraine: a case series.

BackgroundRefractory migraine is a challenging condition with great impact on health related quality of life. Intravenous (IV) ketamine has been previously used to treat various refractory pain conditions. We present a series of patients with refractory migraine treated with intravenous ketamine in the hospital setting.MethodsBased on retrospective chart review, we identified six patients with refractory migraine admitted from 2010 through 2014 for treatment with intravenous ketamine. Ketamine was administered using a standard protocol starting with a dose of 0.1 mg/kg/hr and increased by 0.1 mg/kg/hr every 3 to 4 h as tolerated until the target pain score of 3/10 was achieved and maintained for at least 8 h. Visual Analogue Scale (VAS) scores at time of hospital admission were obtained as well as average baseline VAS scores prior to ketamine infusion. A phone interview was conducted for follow-up of migraine response in the 3 to 6 months following ketamine infusion.ResultsThe study sample had a median age of 36.5 years (range 29–54) and 83% were women. Pre-treatment pain scores ranged from 9 to 10. All patients achieved a target pain level of 3 or less for 8 h; the average ketamine infusion rate at target was 0.34 mg/kg/hour (range 0.12–0.42 mg/kg/hr). One patient reported a transient out-of-body hallucination following an increase in the infusion rate, which resolved after decreasing the rate. There were no other significant side effects.ConclusionIV ketamine was safely administered in the hospital setting to patients with refractory chronic migraine. Treatment was associated with short term improvement in pain severity in 6 of 6 patients with refractory chronic migraine. Prospective placebo-controlled trials are needed to assess short term and long-term efficacy of IV ketamine in refractory chronic migraine.Electronic supplementary materialThe online version of this article (doi:10.1186/s10194-016-0700-3) contains supplementary material, which is available to authorized users.

Sedentary Behavior Inversely Relates to Insulin Sensitivity and Mitochondrial Oxidative Capacity in Inactive Obese Adults

Sedentary time (ST) is associated with increased risk for insulin resistance, metabolic syndrome, and type 2 diabetes. The impact of ST on insulin sensitivity and muscle mitochondrial oxidative capacity, key mediators of the aforementioned metabolic diseases, is not fully understood. PURPOSE: We sought to determine the impact of ST on insulin sensitivity and muscle oxidative capacity in obese, physically inactive adults. METHODS: We studied 19 inactive, obese (35+1 kg/m2), middle aged (54+1 y) adults. We measured insulin sensitivity using a standardized two-stage hyperinsulinemic-eugIycemic clamp. In isolated vastus lateralis muscle mitochondria, we measured state-3 oxygen flux rates (JO2) by high-resolution respirometry using substrates for complex I, I+II, and II. Finally, we measured ST (<100 counts per min) and time spent in moderate to vigorous physical activity (MVPA, >2020 counts per min) using accelerometry. We used multivariate regression analysis to test for associations between ST and insulin sensitivity and muscle oxidative capacity adjusted for age and MVPA. RESULTS: Data are presented as mean + SEM. The average steady-state glucose infusion rate to maintain euglycemia during the high-dose insulin infusion was 8.4+1 mg/kgFFM/min. The average JO2 were 232 + 16 pmols/s/ml (complex I) and 307+16 pmols/s/ml (complex II). The average wear-time adjusted times spent in ST and MVPA were 570+30 min/d (9.5+0.5 h/d) and 20.4+0.5 min/d. The partial correlations between ST and the average glucose infusion rate and JO2 rates adjusted for age and MVPA were -0.62 (p=0.007), -0.51 (p=0.027, for complex I), and -0.32 (p=0.21, for complex II). CONCLUSION: ST inversely correlates with insulin sensitivity and complex I mediated muscle oxidative capacity in inactive, middle-aged, obese adults when adjusted for age and MVPA. We propose that reducing ST will improve insulin sensitivity and muscle oxidative capacity.

Dextrose-containing intraoperative fluid in neonates: a randomized controlled trial.

Glucose requirement in neonates during surgery and the impact of glucose supplementation on neonatal metabolism remain unclear. This study was designed to identify an appropriate perioperative fluid regimen in neonates which maintains carbohydrate and lipid homeostasis. Forty-five neonates undergoing primary repair of a trachea-esophageal fistula were randomly allocated into three groups. During surgery, the neonates received either 1% dextrose in Ringer lactate (RL) (group D1) at 10 ml·kg(-1) ·h(-1) , or 2% dextrose in RL (group D2) at 10 ml·kg(-1) ·h(-1) , or 10% dextrose in N/5 saline at 4 ml·kg(-1) ·h(-1) and replacement fluid with 6 ml·kg(-1) ·h(-1) of RL (group D4). Glucose homeostasis, electrolyte balance, acid-base status, and endocrine and metabolic parameters were compared among the groups during the perioperative period. Blood glucose increased in all the three groups at the end of surgery, with no significant difference in blood glucose and incidence of hyperglycemia (BG > 150 mg·dl(-1) ) among them. At 24 h after surgery, blood glucose and incidence of hyperglycemia was significantly higher in Group D1 compared to Group D4. Base excess, bicarbonate, lactate, and pH showed a significant fall in Group D1. There was no significant difference in serum-free fatty acids, serum beta-hydroxy butyrate, and serum cortisol in three groups. At the end of surgery, serum insulin was significantly lower and glucagon : insulin (G : I) ratio was higher in Group D1 compared to Group D4. All three solutions, when infused at 10 ml·kg(-1) ·h(-1) , are equally effective in maintaining glucose homeostasis, but 1% dextrose-containing fluid promotes catabolism, insulin resistance, rebound hyperglycemia, and acidosis. Therefore, 2-4% dextrose-containing fluids is more suitable compared to 1% dextrose-containing fluids for use during major neonatal surgeries requiring average fluid infusion rate of 10 ml·kg(-1) ·h(-1) .

Anestesia geral inalatória ou total intravenosa associada à anestesia subaracnoidea, em ovinos

Avaliou-se a eficácia e a segurança anestésica em ovinos mantidos sob anestesia geral inalatória com isofluorano ou anestesia total intravenosa com propofol, ambas associadas à anestesia subaracnoidea. Quatorze ovinos foram pré-medicados com 0,3mg.kg-1 de morfina IM, e cinco minutos após, receberam 20mcg.kg-1 de detomidina IV. Posteriormente, foram alocados aleatoriamente em dois grupos: GISO (n=7), os quais foram induzidos à anestesia geral com 0,5mg.kg-1 de diazepam e 5mg.kg-1 de cetamina IV, e mantidos em anestesia geral inalatória com isoflurano diluído em oxigênio a 100%; e GPRO (n=7), induzidos com 4mg.kg-1 de propofol IV seguido inicialmente de infusão contínua na taxa de 0,3mg.kg-1.min-1. Para realização da osteotomia bilateral, todos os animais receberam 0,5mg.kg-1 de ropivacaína 0,75% associado a 0,1mg.kg-1 de morfina pela via subaracnoidea. Houve redução de 40% nos valores médios de frequência cardíaca após sedação em ambos os grupos, permanecendo em média 23% reduzida até o final da avaliação. A pressão arterial média aumentou 16%, após a indução anestésica no GISO, mas se reduziu até o final do procedimento, assim como no GPRO. A EtISO média foi de 0,57V% e a taxa média de infusão do propofol foi de 0,24mg.kg-1.min-1. Os tempos totais de cirurgia, anestesia e extubação foram de 66±9,8, 92±13,8 e 7,0±1,5 minutos no GISO e 56±2,4, 82,9±4,6 e 5,4±1,5 minutos no GPRO, não havendo diferença significativa entre grupos. A manutenção anestésica com isoflurano ou propofol promoveu plano anestésico similar com mínimos efeitos cardiovasculares ou hemogasométricos, que são bem tolerados em ovinos hígidos.

Female Patients Require a Higher Propofol Infusion Rate for Sedation.

Sedation may minimize physiologic and behavioral stress responses. In our facility, the infusion rate of propofol is adjusted according to the bispectral index (BIS) in all cases of implant-related surgery; multivariate analysis of retrospective data enabled us to extract independent factors that affect the dose of propofol in sedation that are considered useful indicators for achieving adequate sedation. The study population comprised all patients undergoing implant-related surgery under intravenous sedation in Okayama University Hospital from April 2009 to March 2013. The infusion rate of propofol was adjusted to maintain the BIS value at 70-80. The outcome was the average infusion rate of propofol, and potential predictor variables were age, sex, body weight, treatment time, and amount of midazolam. Independent variables that affected the average infusion rate of propofol were extracted with multiple regression analysis. One hundred twenty-five subjects were enrolled. In the multiple regression analysis, female sex was shown to be significantly associated with a higher average infusion rate of propofol. Females may require a higher infusion rate of propofol than males to achieve adequate sedation while undergoing implant-related surgery.

Prevalence and potential risk factors of hypokalemia in pediatric patients with diabetic ketoacidosis

Methods Retrospective review of 114 consecutive patient-episodes. Univariate analyses were performed to study any difference in mean between the group with nadir of potassium (Kn) >= 3.0mmol/L from group with Kn < 3.0mmol/L for predictors concerning patients’ demographics, the baseline characteristics, the therapies for DKA (including average insulin infusion rate before Kn), and the pace of recovery from DKA. Predictors deemed statistical significant in univariate analyses were subjected to multivariate analysis.

Passive reporting greatly underestimates the rate of transfusion-associated circulatory overload after platelet transfusion.

Transfusion-associated circulatory overload (TACO) is the second leading cause of reported transfusion-related fatalities in the United States. While its occurrence has been previously investigated after red cell and plasma transfusion, no data are available regarding its association with platelet transfusion. Our goal was to determine the rate of platelet-associated TACO at our university medical centre. This study had retrospective and prospective analyses. The 13-year retrospective analysis served to determine the historical rate of platelet-associated TACO by passive reporting. The 30-day prospective analysis included active surveillance of all non-emergently issued and non-operative platelet recipients ≥16years old with no transfusions in the previous 6h determined by analysis of blood bank product issue records. Data collected included demographics, vital signs pre- and posttransfusion, fluid balances, supplemental oxygen use, reports of dyspnoea, and infusion rates. For the prospective analysis, all variables were collected within 24h of transfusion from the medical record and, when necessary, interviews with care providers and/or patients. In the retrospective analysis, 366 reactions were reported, of which 6 (1·6%) were TACO. The historical rate of TACO was 1:5997 transfused platelet units. During the prospective analysis, 225 eligible patients received a total of 334units of platelets. The average platelet transfusion volume was 261±26ml, and the average infusion rate was 391±198ml/h. Two unreported TACO reactions were discovered and characterized by new-onset hypertension, crackles on lung auscultation, dyspnoea, hypoxia and supplemental oxygen requirements which resolved completely with diuresis. The rate of TACO during this prospective analysis was 1:167 transfused platelet units. Platelet-associated TACO is greatly underestimated by passive reporting in the adult patient population.

Epigallocatechin gallate prevents inflammation by reducing macrophage infiltration and inhibiting tumor necrosis factor-α signaling in the pancreas of rats on a high-fat diet

In this study, we hypothesized that epigallocatechin gallate (EGCG) would suppress inflammation in the pancreas, and thus, we investigated the effects that EGCG administration had in the pancreas of rats fed a high-fat diet (HFD). To test our hypothesis, 30 male Sprague-Dawley rats were divided into 2 groups: normal diet (control) group and HFD group. When there was a significant difference in body weight between the 2 groups (P < .05), the HFD group was further divided into 2 subgroups: the HFD group (HFD, n = 10, 16 weeks) and the EGCG group (HFD + 3.2 g/kg EGCG, n = 10, 16 weeks). Metabolite levels and the expression of inflammatory markers (tumor necrosis factor alpha [TNF-α], interleukin 6 [IL-6], and toll-like receptor 4) were measured using standard biochemical techniques. Insulin secretion and pancreatic histology were also evaluated. Epigallocatechin gallate significantly decreased fasting insulin levels as well as the homeostasis model assessment–insulin resistance index. In the HFD group, the average glucose infusion rate and the TNF-α and IL-6 levels increased, whereas toll-like receptor 4 and TNF receptor-associated factor-6 did not. A pathologic analysis of pancreatic tissue revealed an increase in inflammatory TNF-α and infiltrating CD68+ macrophages in the islets of the HFD rats, but rarely is this observed in the in the HFD + EGCG rats. Overall, these data suggest that EGCG suppresses inflammation, partially reverses metabolic abnormalities, and ultimately increases insulin sensitivity in the pancreas of HFD rats.

The Glucoregulatory Benefits of Glucagon-Like Peptide-1 (7-36) Amide Infusion During Intensive Insulin Therapy in Critically Ill Surgical Patients

Intensive insulin therapy for tight glycemic control in critically ill surgical patients has been shown to reduce mortality; however, intensive insulin therapy is associated with iatrogenic hypoglycemia and increased variability of blood glucose levels. The incretin glucagon-like peptide-1 (7-36) amide is both insulinotropic and insulinomimetic and has been suggested as an adjunct to improve glycemic control in critically ill patients. We hypothesized that the addition of continuous infusion of glucagon-like peptide-1 to intensive insulin therapy would result in better glucose control, reduced requirement of exogenous insulin administration, and fewer hypoglycemic events. Prospective, randomized, double-blind, placebo-controlled clinical trial. Surgical or burn ICU. Eighteen patients who required intensive insulin therapy. A 72-hour continuous infusion of either glucagon-like peptide-1 (1.5 pmol/kg/min) or normal saline plus intensive insulin therapy. The glucagon-like peptide-1 cohort (n = 9) and saline cohort (n = 9) were similar in age, Acute Physiology and Chronic Health Evaluation score, and history of diabetes. Blood glucose levels in the glucagon-like peptide-1 group were better controlled with much less variability. The coefficient of variation of blood glucose ranged from 7.2% to 30.4% in the glucagon-like peptide-1 group and from 19.8% to 56.8% in saline group. The mean blood glucose coefficient of variation for the glucagon-like peptide-1 and saline groups was 18.0% ± 2.7% and 30.3% ± 4.0% (p = 0.010), respectively. The 72-hour average insulin infusion rates were 3.37 ± 0.61 and 4.57 ± 1.18 U/hr (p = not significant). The incidents of hypoglycemia (≤ 2.78 mmol/L) in both groups were low (one in the glucagon-like peptide-1 group, three in the saline group). Glucagon-like peptide-1 (7-36) amide is a safe and efficacious form of adjunct therapy in patients with hyperglycemia in the surgical ICU setting. Improved stability of blood glucose is a favorable outcome, which enhances the safety of intensive insulin therapy. Larger studies of this potentially valuable therapy for glycemic control in the ICU are justified.

Evidence-Based Morphine Dosing for Postoperative Neonates and Infants

From a previously validated paediatric population pharmacokinetic model, it was derived that non-linear morphine maintenance doses of 5 μg/kg(1.5)/h, with a 50 % dose reduction in neonates with a postnatal age (PNA) <10 days, yield similar morphine and metabolite concentrations across patients younger than 3 years. Compared with traditional dosing, this model-derived dosing regimen yields significantly reduced doses in neonates aged <10 days. Concentration predictions of the population model were prospectively evaluated in postoperative term neonates and infants up to the age of 1 year who received morphine doses according to the model-derived algorithm. The efficacy of this dosing algorithm was evaluated using morphine rescue medication and actual average infusion rates. Morphine and metabolite concentrations were accurately predicted by the paediatric pharmacokinetic morphine model. With regard to efficacy, 5 out of 18 neonates (27.8 %) with a PNA of <10 days needed rescue medication versus 18 of the 20 older patients (90 %) (p = 0.06). The median (interquartile range [IQR]) total morphine rescue dose was 0 (0-20) μg/kg in younger patients versus 193 (19-362) μg/kg in older patients (p = 0.003). The median (IQR) actual average morphine infusion rate was 4.4 (4.0-4.8) μg/kg/h in younger patients versus 14.4 (11.3-23.4) μg/kg/h in older patients (p < 0.001). Morphine paediatric dosing algorithms corrected for pharmacokinetic differences alone yield effective doses that prevent over-dosing for neonates with a PNA <10 days. The fact that many neonates and infants with a PNA ≥10 days still required rescue medication warrants pharmacodynamic studies to further optimize the dosing algorithm for these patients.

Is Propofol a Friend or a Foe of the Pediatric Intensivist? Description of Propofol Use in a PICU*

The primary objective is to describe the practice patterns of nonprocedural propofol use in a single-center referral PICU. The secondary objective is to describe the rate of concordance of propofol use with the PICU local practice of a maximum mean rate of 4 mg/kg/hr and a maximum duration of 24 hours and to assess for signs and symptoms of propofol infusion syndrome. Retrospective descriptive cohort study. PICU of a tertiary care teaching hospital and referral hospital for the Western Canada. Children 1 month to 17 years old who received a nonprocedural propofol infusion between January 1, 2009, and December 31, 2009. None. Two hundred twenty-three infusions (representing 210 unique patients) were included in the study. The median average infusion rate (interquartile range) including boluses was 2.7 mg/kg/hr (1.9-3.6 mg/kg/hr), and the mean infusion duration (SD) was 10.3 hours (6.7 hr). Eighty-seven percent and 98% of infusions were concordant with PICU intensivists self-reported practice maximum rate and duration, respectively. No cases of propofol-related infusion syndrome or deaths associated with propofol infusions were identified. The use of propofol infusions was in concordance with PICU local practice, and propofol infusion syndrome did not developed in patients. In agreement with previous recommendations, propofol infusions in the PICU appear to be safe when limiting doses to 4 mg/kg/hr and for less than 24 hours; however, appropriate monitoring of adverse effects is still warranted due to absence of robust evidence.

Epigallocatechin gallate improves insulin signaling by decreasing toll‐like receptor 4 (TLR4) activity in adipose tissues of high‐fat diet rats

In this study, we investigated the beneficial effects and the underlying mechanism of epigallocatechin gallate (EGCG) in adipose tissues of rats fed with a high-fat diet (HFD). Fasting plasma insulin, epididymal fat coefficient and free fatty acids, homeostasis model assessment-insulin resistance index, and the average glucose infusion rate were determined. EGCG significantly decreased free fatty acids, fasting insulin, homeostasis model assessment-insulin resistance index, and epididymal fat coefficient, and increased glucose infusion rate in HFD group. The levels of toll-like receptor 4, TNF receptor associated factor 6, inhibitor-kappa-B kinase β, p-nuclear factor κB, tumor necrosis factor α, and IL-6 in the EGCG group were all significantly lower than the HFD control group. EGCG also decreased the level of phosphorylated insulin receptor substrate 1 and increased phosphoinositide-3-kinase and glucose transporter isoform 4 in the HFD group. Decreased macrophage infiltration was in EGCG group versus HFD group, and the protein level of CD68 in EGCG group was also significantly lower than that of HFD group. EGCG attenuated inflammation by decreasing the content of macrophages, interfered the toll-like receptor 4 mediated inflammatory response pathway, thus, improving insulin signaling in adipose tissues.