Intravenous Loading Research Articles

Can high-dose tranexamic acid have a role during transurethral resection of the prostate in large prostates? A randomised controlled trial

ABSTRACT Objective: To assess the efficacy and safety of high-dose tranexamic acid (TXA) during bipolar transurethral resection of the prostate (B-TURP) in patients with large prostates compared to placebo. Patients and methods: From February 2018 to May 2020, 204 patients with enlarged prostates of 80–130 g and in need of surgical intervention were randomised into two groups. Patients in Group A underwent B-TURP and received TXA as an intravenous loading dose of 50 mg/kg over 20 min before induction of anaesthesia followed by a maintenance infusion of 5 mg/kg/h until resection was completed. The patients in Group B (placebo) received a saline infusion of a similar volume. Results: There was highly significant drop in haemoglobin in the placebo group at 4- and 24-h postoperatively compared with the TXA group (P < 0.001). However, there was no significant difference in the blood transfusion rate between the two groups with five patients (5.5%) in the placebo group and four (4.2%) in the TXA group requiring a transfusion (P = 0.74). The procedural time was significantly less in the TXA group vs the control group, at a mean (SD) of 79.93 (22.18) vs 90.91 (21.4) min (P = 0.001). Also, the intraoperative irrigation fluid volume and postoperative irrigation duration were significantly less in the TXA group vs the control group, at a mean (SD) of 19.21 (3.13) vs 23.05 (3.8) L and 14.75 (5.15) vs 18.33 (5.96) h, respectively (P = 0.001). Catheterisation and hospital stay durations were comparable between both groups (P = 0.384 and P = 0.388, respectively). No complications were recorded with use of high-dose TXA. Conclusion: High-dose TXA was effective in controlling blood loss during B-TURP in patients with large prostates, with no adverse drug reactions.

Combining perampanel and ketamine in super refractory post-traumatic status epilepticus: A case report

Status Epilepticus (SE) is a condition resulting either from the failure of seizure termination mechanisms or from the abnormal activation of prolonged seizure mechanisms. It represents a life-threatening medical emergency associated with high morbidity and mortality that requires prompt diagnosis and treatment. SE treatment begins with a quick-acting benzodiazepine, followed by intravenous (IV) loading and a continuous infusion of antiseizure medications (ASMs). The failure of first- and second-line treatments is defined as “refractory SE” (RSE) and requires infusion of IV anaesthetics.

When MINMOD Artifactually Interprets Strong Insulin Secretion as Weak Insulin Action

We address a problem with the Bergman-Cobelli Minimal Model, which has been used for 40 years to estimate SI during an intravenous glucose tolerance test (IVGTT). During the IVGTT blood glucose and insulin concentrations are measured in response to an acute intravenous glucose load. Insulin secretion is often assessed by the area under the insulin curve during the first few minutes (Acute Insulin Response, AIR). The issue addressed here is that we have found in simulated IVGTTs, representing certain contexts, Minimal Model estimates of SI are inversely related to AIR, resulting in artifactually lower SI. This may apply to Minimal Model studies reporting lower SI in Blacks than in Whites, a putative explanation for increased risk of T2D in Blacks. The hyperinsulinemic euglycemic clamp (HIEC), the reference method for assessing insulin sensitivity, by contrast generally does not show differences in insulin sensitivity between these groups. The reason for this difficulty is that glucose rises rapidly at the start of the IVGTT and reaches levels independent of SI, whereas insulin during this time is determined by AIR. The minimal model in effect interprets this combination as low insulin sensitivity even when actual insulin sensitivity is unchanged. This happens in particular when high AIR results from increased number of readily releasable insulin granules, which may occur in Blacks. We conclude that caution should be taken when comparing estimates of SI between Blacks and Whites.

An Analysis of Glucose Effectiveness in Subjects With or Without Type 2 Diabetes via Hierarchical Modeling.

Glucose effectiveness, defined as the ability of glucose itself to increase glucose utilization and inhibit hepatic glucose production, is an important mechanism maintaining normoglycemia. We conducted a minimal modeling analysis of glucose effectiveness at zero insulin (GEZI) using intravenous glucose tolerance test data from subjects with type 2 diabetes (T2D, n=154) and non-diabetic (ND) subjects (n=343). A hierarchical statistical analysis was performed, which provided a formal mechanism for pooling the data from all study subjects, to yield a single composite population model that quantifies the role of subject specific characteristics such as weight, height, age, sex, and glucose tolerance. Based on the resulting composite population model, GEZI was reduced from 0.021 min–1 (standard error – 0.00078 min–1) in the ND population to 0.011 min–1 (standard error – 0.00045 min–1) in T2D. The resulting model was also employed to calculate the proportion of the non–insulin-dependent net glucose uptake in each subject receiving an intravenous glucose load. Based on individual parameter estimates, the fraction of total glucose disposal independent of insulin was 72.8% ± 12.0% in the 238 ND subjects over the course of the experiment, indicating the major contribution to the whole-body glucose clearance under non-diabetic conditions. This fraction was significantly reduced to 48.8% ± 16.9% in the 30 T2D subjects, although still accounting for approximately half of the total in the T2D population based on our modeling analysis. Given the potential application of glucose effectiveness as a predictor of glucose intolerance and as a potential therapeutic target for treating diabetes, more investigations of glucose effectiveness in other disease conditions can be conducted using the hierarchical modeling framework reported herein.

No increased acute kidney injury rate through giving an intravenous colistin loading dose in pediatric patients

ObjectivesA colistin loading dose is required to achieve adequate drug exposure for the treatment of multidrug-resistant Gram-negative bacteria. However, data on acute kidney injury (AKI) rates associated with this approach in children have been unavailable. The aim of this study was to examine AKI rates in children who were prescribed a colistin loading dose. MethodsA retrospective study was conducted in patients aged 1 month to 18 years who had received intravenous colistin for ≥48 h. Loading dose (LD) was defined as colistin methanesulfonate at 4–5 mg of colistin base activity/kg/dose. AKI was defined according to KDIGO serum creatinine (SCr) criteria — SCr ≥ 1.5 times the baseline, measured 3–7 days after colistin initiation. Augmented renal clearance (ARC) was defined as an estimated glomerular filtration rate (eGFR) >150 mL/min/1.73 m2. The rates of AKI were compared between children receiving or not receiving an LD, and between different eGFR groups. ResultsIn total, 181 children were enrolled. The mean age was 4.3 years (95% confidence interval [CI], 3.6–4.9 years). Ninety-five of the subjects (52.5%) were male. There were 157 children with a baseline eGFR of ≥ 80 mL/min/1.73 m2. The overall AKI rate within the first week in this group was 20.4% (95% CI, 14.4–27.6%): LD, 16.1% vs no LD, 23.2% (p = 0.29). Subgroup analysis, excluding patients with ARC, showed a lower AKI rate of 12.8% (95% CI, 6.8–21.3%): LD, 9.7% vs no LD, 14.3% (p = 0.53). ConclusionsAKI rate was not different among children who received an intravenous colistin loading dose. This approach should be implemented to ensure the necessary drug exposure required for good treatment outcomes.

Abstract PD3-02: Final analysis of PERTAIN: A randomized, two-arm, open-label, multicenter phase II trial assessing the efficacy and safety of first-line pertuzumab given in combination with trastuzumab plus an aromatase inhibitor in patients with HER2-positive and hormone receptor-positive metastatic or locally advanced breast cancer

Abstract Background The role of bidirectional cross talk between the HER2 and estrogen receptors in resistance to anti-HER2 and endocrine therapy has been studied extensively (Kaufman et al. J Clin Oncol 2009; Arpino et al. J Natl Cancer Inst 2007). The CLEOPATRA study showed that first-line pertuzumab (P) + trastuzumab (H) + docetaxel (T) improved progression-free survival (PFS) and overall survival (OS) significantly compared with placebo + H + T in patients (pts) with HER2-positive metastatic BC (MBC) (Baselga et al. N Engl J Med 2012; Swain et al. Lancet Oncol 2013; N Engl J Med 2015; N Engl J Med 2020). PERTAIN (NCT01491737) was the first randomized phase II trial to assess the addition of P to H + an aromatase inhibitor (AI) ± induction chemotherapy for the first-line treatment of pts with HER2-positive and hormone receptor-positive MBC or locally advanced BC (LABC). PERTAIN met its primary PFS endpoint at 31 months’ median follow-up, with a potentially enhanced effect in some groups, such as pts who did not receive induction chemotherapy (Rimawi et al. J Clin Oncol 2018). We present the final analysis at more than 6 years’ median follow-up, including updated PFS, mature OS (secondary endpoint), and updated safety. Methods Pts were randomized 1:1 to P + H + AI (Arm A) or H + AI (Arm B). P was given as an 840 mg intravenous (IV) loading dose followed by 420 mg every 3 weeks (q3w); H IV, at 8 mg/kg followed by 6 mg/kg q3w; anastrozole, at 1 mg daily; or letrozole, at 2.5 mg daily. Induction IV chemotherapy with T q3w or weekly paclitaxel could be given for 18-24 weeks at the investigator’s discretion before the start of endocrine therapy. Treatment was given until disease progression or unacceptable toxicity. Pts were stratified by induction chemotherapy (yes/no) and time since adjuvant hormone therapy (&amp;lt;12 months, ≥12 months, no adjuvant hormone therapy). Time-to-event endpoints were analyzed using Kaplan-Meier methods. Results Pts were randomized across 71 sites and 8 countries between Feb 2012 and Oct 2014. Intent-to-treat populations were 129 pts per arm; safety populations, 127 and 124 in Arms A and B, respectively; induction chemotherapy was received by 75 and 71 pts, respectively. Baseline demographics and disease characteristics were generally balanced between arms. Efficacy results are shown in the table. One hundred twenty-two pts per arm reported adverse events (AEs) at any grade (96.1% in Arm A; 98.4% in Arm B); 72 (56.7%) and 51 pts (41.1%) had grade ≥3 AEs, the most common grade ≥3 AEs (≥5.0%; Arm A vs. Arm B) being hypertension (11.8% vs. 10.5%), diarrhea (9.4% vs. 2.4%), and neutropenia (3.1% vs. 7.3%). Conclusions With a median follow-up of more than 6 years at final analysis, the PFS benefit of adding P to H + an AI was maintained. OS was similar between arms. A potentially enhanced treatment effect was observed by addition of P to H + an AI in pts who did not receive induction chemotherapy after randomization. There were no new safety concerns at final analysis. Overall, PERTAIN provides additional evidence on the role of P + H in the first-line treatment of HER2-positive MBC/LABC and suggests that some pts benefit from P + H + AI without induction chemotherapy. Arm AArm BMedian PFS, mo HR (95% CI)ITT21160.7 (0.5-0.9) p=0.006With induction17170.7 (0.5-1.0) p=0.08No induction27120.7 (0.4-1.0) p=0.07Median OS, mo HR (95% CI)ITT60571.1 (0.7-1.5) p=0.8With induction59661.2 (0.7-1.9) p=0.5No induction65540.9 (0.5-1.6) p=0.7CI, confidence interval; HR, hazard ratio; ITT, intent-to-treat; mo, months. Citation Format: Grazia Arpino, Juan de la Haba-Rodriguez, Jean-Marc Ferrero, Sabino De Placido, Dirk Klingbiel, Valentine Revelant, Christine Wohlfarth, Raf Poppe, Mothaffar F Rimawi. Final analysis of PERTAIN: A randomized, two-arm, open-label, multicenter phase II trial assessing the efficacy and safety of first-line pertuzumab given in combination with trastuzumab plus an aromatase inhibitor in patients with HER2-positive and hormone receptor-positive metastatic or locally advanced breast cancer [abstract]. In: Proceedings of the 2020 San Antonio Breast Cancer Virtual Symposium; 2020 Dec 8-11; San Antonio, TX. Philadelphia (PA): AACR; Cancer Res 2021;81(4 Suppl):Abstract nr PD3-02.

Collecting duct-specific knockout of sphingosine-1-phosphate receptor 1 aggravates DOCA-salt hypertension in mice.

We have previously reported that renal medullary sphingosine-1-phosphate (S1P) regulates sodium excretion via the S1P type-1 receptor (S1PR1). As S1PR1 is predominantly expressed in collecting ducts (CD), the present study tested the hypothesis that the CD-S1PR1 pathway plays a critical role in sodium excretion and contributes to salt-sensitive hypertension. CD-specific S1PR1 knockout mice were generated by crossing aquaporin-2-Cre mice with S1PR1-floxed mice. Renal sodium excretion and arterial pressure were compared between wild type and KO mice in response to high-salt challenges and treatment of deoxycorticosterone acetate (DOCA) salt. Protein levels of renal medullary S1PR1 were increased by 100% after high-salt intake, whereas DOCA treatment with high-salt intake blocked the increase of S1PR1 levels. Urinary sodium excretions in knockout mice were decreased by 60% compared with wild type mice after acute intravenous sodium loading (0.84 ± 0.16 vs. 2.22 ± 0.62 μmole/min per g kwt). The pressure natriuresis was impaired in knockout mice compared with wild type mice (4.32 ± 1.04 vs. 8.73 ± 0.19 μmole/min per g kwt). The chronic high-salt intake-induced positive sodium balance was enhanced in knockout mice compared with wild type mice (5.27 ± 0.39 vs. 2.38 ± 1.04 mmol/100 g BW per 24 h). After 10-day DOCA-salt treatment, knockout mice developed more severe hypertension than wild type mice (SBP 142 ± 8 vs. 115 ± 4 mmHg). The deletion of CD-S1PR1 reduced sodium excretion, promoted sodium retention, and accelerated DOCA-salt-induced salt-sensitive hypertension, suggesting that the CD-S1PR1 signaling is an important antihypertensive pathway by promoting sodium excretion and that impairment of renal medullary S1PR1 may represent a novel mechanism for salt-sensitive hypertension.

1008. Disease Severity Impact on Long-Term Virologic Response to Ibalizumab in Expanded Access Protocol (TMB-311)

BackgroundThe principal goal of antiretroviral therapy (ART) is durable suppression of HIV RNA. In treatment-experienced (TE) patients, ongoing viremia can lead to further accumulation of drug resistance, increased morbidity and mortality. ART efficacy often depends on HIV disease severity; therefore, we sought to assess its impact on long-term virologic suppression in patients treated with Ibalizumab (IBA), the first long-acting, post-attachment inhibitor approved for multi-drug resistant (MDR) HIV-1 treatment.MethodsIn TMB-301, a Phase 3 study, 40 TE patients with viral load (VL) >1000 copies/mL (c/mL) received an intravenous (IV) loading dose of IBA (2000mg) followed by maintenance doses (800mg IV) every 2 weeks combined with an optimized background regimen. Patients who completed TMB-301 in the US (n=27) continued to an expanded access protocol TMB-311. To determine the impact of baseline (BL) disease on long-term virologic response, we conducted an on-treatment analysis stratified by BL VL and CD4 count up to week 96. Differences in the proportion of suppressed (< 50 c/mL) individuals among the strata were assessed by Fisher’s exact test.ResultsMedian BL VL and CD4 count were 35,350 c/mL and 73 cells/mL, respectively. The number of patients in the VL strata were 11, 17 and 12 for VL < 10,000, 10,000-70,000, and >70,000 c/mL, respectively. There were 12, 10, 5 and 13 patients in the subgroups with CD4 count < 10, 10-100, >100-200 and >200 cells/µL. Population disease severity was reflected by four deaths (unrelated to study drug). Overall, the proportion of suppressed patients increased from 55% at week 24 (n=31) to 75% for patients remaining on treatment for 96 weeks (n=20). Median VL decrease was 2.9 log10 c/mL. Notably, no statistically significant differences were found across groups. Among patients with advanced HIV disease, 66.7% with CD4 count < 10 cells/mL and 71.4% with VL >70,000 c/mL at BL remained fully suppressed at week 96.ConclusionIn TE patients with advanced HIV disease, maximal viral suppression with IBA was observed regardless of BL CD4 or VL strata if patients remained on treatment. This demonstrates that TE patients across the spectrum of HIV disease, can achieve viral suppression by using drugs with a new mechanism of action.Disclosures Princy Kumar, MD, Gilead Sciences Inc. (Scientific Research Study Investigator) Jason Leider, MD, PhD, THERA (Speaker’s Bureau) Jihad Slim, MD, Abbvie (Speaker’s Bureau)Gilead (Speaker’s Bureau)Jansen (Speaker’s Bureau)Merck (Speaker’s Bureau)ViiV (Speaker’s Bureau) Graeme Moyle, MD, Theratechnologies (Consultant) Maurice Leonard, PhD, Theratechnologies Europe Ltd (Employee, Shareholder) R Brandon Cash, PharmD, Theratechnologies (Employee) Steven Weinheimer, PhD, TaiMed Biologics USA (Employee) Pedro Mesquita, PhD, Theratechnologies, Inc. (Employee)

The Effect of Hypotensive Anesthesia on Hemoglobin Levels during Total Knee Arthroplasty.

Introduction: Hypotensive epidural anesthesia (HEA) is used in total joint arthroplasty as a safe and effective blood-saving modality. In order to maintain the blood pressure and heart rate patients, receive 1000 to 1500 mL of lactated Ringer’s solution during surgery. While HEA reduces the intraoperative blood loss, the effect of intravenous fluid loading on hemoglobin levels is not fully understood. The current study investigates the effect of HEA on perioperative hemoglobin levels. Materials and Methods: The study included 35 patients operated on by a single surgeon undergoing primary total knee arthroplasty under HEA. Intraoperatively, at least 300 mL of intravenous fluid were given every 15 min over the first 60 min after HEA. Blood samples were drawn before entering the operating room, after HEA, as well as after inflation of the tourniquet, every 15 min thereafter, as well as in the recovery room and on postoperative days one and two. In addition, fluid in- and outtake was recorded. Results: Patients received a mean 1275 mL during the 60 min of tourniquet time. The mean arterial pressure (MAP) 5 min after HEA dropped to 60 mmHg and reached a constant level of around 58 mmHg 15 min after HEA. The average hemoglobin level dropped from 13.9 g/dL prior to HEA, to 12.5 g/dL immediately after HEA (p < 0.001). Intraoperatively the hemoglobin level dropped further and reached 11.8 g/dL at 60 min in the absence of blood loss. Conclusions: Hypotensive epidural anesthesia and the resulting fluid substitution resulted in an average hemoglobin drop of 2.1 g/dL within the first 60 min. This needs to be taken into account when evaluating the need for blood transfusions after primary joint replacement surgery under HEA.

The Effect of Intraoperative Magnesium Sulphate Infusion on Emergence Agitation after Ambulatory Ophthalmic Surgery in Children

This study investigated whether intraoperative infusion of magnesium sulphate reduces the incidence of emergence agitation (EA) in paediatric patients who undergo ambulatory ophthalmic surgery using the Paediatric Anaesthesia Emergence Delirium (PAED) scale. Ninety-two paediatric patients who were scheduled for elective ophthalmic surgery were randomly allocated to two groups: control or magnesium. In the magnesium group, patients received an initial intravenous loading dose of 30 mg/kg of 10% solution of magnesium sulphate over 10 min and then a continuous infusion of 10 mg/kg×h during the surgery. In the control group, an equal volume of 0.9% isotonic saline was administered in the same way as in the magnesium group. The PAED scale was assessed at 15-min intervals until the PAED score reached below 10 at the postanaesthetic care unit. EA was defined as a PAED score of 10 or higher. Of the 86 patients recruited, 44 and 42 were allocated to the control and magnesium groups, respectively. The incidence of EA was 77.3% in the control group and 57.1% in the magnesium group (odds ratio, 0.392; 95% confidence interval, 0.154 to 0.997; p = 0.046). The intraoperative infusion of magnesium sulphate significantly reduced the incidence of EA.

Hyperchloremia in critically ill patients: association with outcomes and prediction using electronic health record data

BackgroundIncreased chloride in the context of intravenous fluid chloride load and serum chloride levels (hyperchloremia) have previously been associated with increased morbidity and mortality in select subpopulations of intensive care unit (ICU) patients (e.g patients with sepsis). Here, we study the general ICU population of the Medical Information Mart for Intensive Care III (MIMIC-III) database to corroborate these associations, and propose a supervised learning model for the prediction of hyperchloremia in ICU patients.MethodsWe assessed hyperchloremia and chloride load and their associations with several outcomes (ICU mortality, new acute kidney injury [AKI] by day 7, and multiple organ dysfunction syndrome [MODS] on day 7) using regression analysis. Four predictive supervised learning classifiers were trained to predict hyperchloremia using features representative of clinical records from the first 24h of adult ICU stays.ResultsHyperchloremia was shown to have an independent association with increased odds of ICU mortality, new AKI by day 7, and MODS on day 7. High chloride load was also associated with increased odds of ICU mortality. Our best performing supervised learning model predicted second-day hyperchloremia with an AUC of 0.76 and a number needed to alert (NNA) of 7—a clinically-actionable rate.ConclusionsOur results support the use of predictive models to aid clinicians in monitoring for and preventing hyperchloremia in high-risk patients and offers an opportunity to improve patient outcomes.

Cut-off Values and Clinical Utility of Surrogate Markers for Insulin Resistance and Beta-Cell Function to Identify Metabolic Syndrome and Its Components among Southern Indian Adults.

BackgroundInsulin resistance (IR) is a collective clinical entity that exacerbates metabolic syndrome (MetS). As the gold-standard test to quantify IR involves intravenous insulin loading and repeated blood glucose monitoring, many indices have been developed for IR assessment for convenience. This study tested the ideal cut-off values and clinical utility of IR indices in identifying MetS.MethodsWe recruited 150 subjects, 75 MetS patients and 75 healthy controls, then obtained written informed consent to participate in this study. We collected fasting blood samples for glucose and lipid profiles and calculated nineteen indices of IR and insulin secretion using validated formulae. We determined the precision of these IR indices using the area under the curve (AUC) in a receiver operating characteristic analysis.ResultsSubjects with MetS have significantly higher IR coupled with lower insulin sensitivity and beta-cell function than controls. Among the surrogate markers of IR tested, the homeostatic model assessment of insulin resistance (HOMA-IR), HOMA-adiponectin (HOMA-AD), triglyceride-glucose (TyG) index, HOMA-1%S (insulin sensitivity), quantitative insulin sensitivity check index (QUICKI), McAuley index, single-point insulin sensitivity estimator (SPISE), and HOMA-2%B (beta-cell function) showed the highest AUC values for detecting MetS.ConclusionOur study results suggest that the ideal cut-off and AUC values identified for HOMA-IR, HOMA-AD, the TyG index, HOMA-1%S, QUICKI, the McAuley index, SPISE, and HOMA-2%B offer a clinical approach to the early detection and risk stratification for MetS among people in southern India.

Abstract 13788: Acute Administration of Nicotine Induces Transient Elevation of Blood Pressure and Increases Myocardial Infarct Size in an Acute Myocardial Ischemia/reperfusion Rat Model

Introduction: Nicotine is a major bioactive component in tobacco cigarettes and electronic cigarettes. Despite the fact that smokers are at higher risk of experiencing an acute myocardial infarction (AMI), there are few studies that have examined the acute effects of nicotine on AMI.To address this issue, our present study was to examine the acute effects of nicotine on myocardial infarct size, no reflow, cardiac hemodynamics and cardiac function in a rat myocardial infarct model. Methods: Forty-six female Sprague-Dawley rats were randomly divided into nicotine group and control group (n=23/group) and received an intravenous loading dose of nicotine at 2.0 μg/kg/min or saline for 30 minutes before starting coronary artery occlusion, then followed by a maintenance dose 0.35 μg/kg/min of nicotine to the end of 3.5 hours of occlusion (30 minutes) and reperfusion (3 hours). Results: At baseline, there were no difference between the two study groups, in systolic blood pressure (BP in mmHg) (nicotine, 69.0±2.7; control, 69.3±4.4; p &gt; 0.05), or diastolic BP (nicotine, 45.7±3.2; control, 48.2±4.2; p &gt; 0.05). Nicotine initially increased systolic BP (nicotine, 97.0±8.6; control, 69.2±3.3, p &lt;0.05) and diastolic BP (nicotine, 65.6±6.4; control, 47.4±3.1, p &lt; 0.01) at 10 minutes after starting injection of the loading dose; pressures dropped to control levels in both groups at 30 minutes. During occlusion/reperfusion, the BP and heart rate were not altered by nicotine. Nicotine significantly increased myocardial infarct size as a percentage of the ischemic risk zone compared to the controls (nicotine, 54.9 ± 1.9 %; control, 48.6 ± 2.7 %, p &lt; 0.05), but nicotine did not affect the no-reflow size (nicotine, 34.8 ± 3.10 %; control, 33.7 ± 3.0%, p &gt; 0.05). Nicotine did not alter fractional shortening assessed by echocardiography. Conclusions: Nicotine infusion can transiently increase blood pressure in anesthetized rats. During coronary occlusion and reperfusion, nicotine increased myocardial infarct size, but did not affect hemodynamics or fractional shortening, suggesting that the increase in infarct size was not simply due to an increase in oxygen demand due to altered afterload, heart rate or contractility, but may reflect a more direct effect on the myocardium.

Nutritional Status Assessment in ICU Patients Using Ultrasound Imaging of Muscles and Subcutaneous Fat

Ultrasound imaging of muscles and subcutaneous fat has been used in recent years to assess the nutritional status, but there are no common approaches for selecting muscles for it.The aim of the study was to examine the variability of thickness of different muscles and subcutaneous fat using ultrasonography to identify optimal cutaneous and muscle landmarks for the assessment of nutritional status.Materials and methods. It was a prospective observational study with participation of 14 patients. All patients underwent ultrasound examination of thickness of the following muscles: m. rectus femoris; m. tibialis anterior; m. biceps brachii; m. deltoideus and m. sternocleidomastoideus, as well as the thickness of skin and subcutaneous fat over the muscles. The ultrasound assessment was done on admission to ICU, on days 7, 14, 21, 28, 42. On days 7, 14 and 21 the intravenous load test of 1000 ml of 0.9% sodium chloride solution was performed. On days 5 and 10 the test with the patients in the lateral decubitus position was carried out.Results. We found that m. tibialis anterior changed its size when patients were turned laterally by 2%, m. deltoideus by 6%, m. sternocleidomastoideus by 10%, m. rectus femoris by 20.5%, and m. biceps brachii by 26%. After infusion of 1,000 ml of 0,9% sodium chloride solution, the variability of m. tibialis anterior size was 2%, m. deltoideus 2%, m. sternocleidomastoideus 6%, m. biceps brachii 8%, m. rectus femoris 12%.The thickness of subcutaneous fat over m. biceps brachii and m. rectus femoris changed more than the anteroposterior size of the muscles (P&lt;0.05).Conclusion. The m. deltoideus and m. tibialis anterior are optimal for ultrasound assessment of the nutritional status because their size is less affected by the patient's positioning and infusion therapy. Intravenous fluid infusion increases the variability of subcutaneous fat thickness.

Early Initiation of Treatment with Rivipansel for Acute Vaso-Occlusive Crisis in Sickle Cell Disease (SCD) Achieves Earlier Discontinuation of IV Opioids and Shorter Hospital Stay: Reset Clinical Trial Analysis

Early Initiation of Treatment with Rivipansel for Acute Vaso-Occlusive Crisis in Sickle Cell Disease (SCD) Achieves Earlier Discontinuation of IV Opioids and Shorter Hospital Stay: Reset Clinical Trial Analysis

Crovalimab for Treatment of Patients with Paroxysmal Nocturnal Hemoglobinuria and Complement C5 Polymorphism - Experience from the Phase I/II COMPOSER Study

Crovalimab for Treatment of Patients with Paroxysmal Nocturnal Hemoglobinuria and Complement C5 Polymorphism - Experience from the Phase I/II COMPOSER Study

COMPOSER Part 4: An Optimized Dosing Strategy for Crovalimab in the Treatment of Complement Inhibitor-Naïve or -Experienced Patients with Paroxysmal Nocturnal Hemoglobinuria

COMPOSER Part 4: An Optimized Dosing Strategy for Crovalimab in the Treatment of Complement Inhibitor-Naïve or -Experienced Patients with Paroxysmal Nocturnal Hemoglobinuria

Factors related to passing the safety fast test among neonates with hypoglycaemia in the neonatal intensive care unit.

To investigate the success rates and predictors of safety fast test among neonates admitted to the neonatal intensive care unit for hypoglycaemia. A retrospective review of neonates transferred from the newborn nursery unit to the neonatal intensive care unit for intravenous dextrose therapy for hypoglycaemia from January 2016 to June 2019. Neonatal clinical and demographic variables were abstracted from the medical records. A successful safety fast test was defined by blood glucose >60 mg/dL (3.3 mmol/L) at 3, 4, 5 and 6 h after a feed. Of the 76 neonates who had a safety fast test, 80% passed on their first attempt. Neonates who passed the safety fast test were less likely to be premature/small for gestational age (54.1% vs. 92.9%, P = 0.03), required less maximum glucose infusion rate (median 6 vs. 7 mg/kg/min; P = 0.04), and were younger at fasting challenge (median 5 vs. 9 days; P = 0.02), required lower overall intravenous glucose load (median 12 vs. 24 g/kg; P = 0.006). Safety fast test may be a useful tool evaluating discharge readiness of neonates with persistent hypoglycaemia.

Acute administration of nicotine induces transient elevation of blood pressure and increases myocardial infarct size in rats

AimsWe investigated the acute effects of nicotine on myocardial infarct size, no reflow, hemodynamics and cardiac function in an acute myocardial ischemia and reperfusion infarction rat model. Main methodsFemale Sprague-Dawley rats (n = 23/group) received an intravenous loading dose of nicotine at 2.0 μg/kg/min or saline control for 30 min before starting coronary artery occlusion, then followed by a maintenance dose 0.35 μg/kg/min of nicotine to the end of 30 min occlusion and 3 h reperfusion. Key findingsAt baseline, there was no difference in systolic blood pressure (BP in mmHg) (nicotine, 69.0 ± 2.7; control, 69.3 ± 4.4; p = NS) or diastolic BP (nicotine, 45.7 ± 3.2; control, 48.2 ± 4.2; p = NS) between groups. Nicotine administration initially increased systolic BP (nicotine, 97.0 ± 8.6; control, 69.2 ± 3.3, p < 0.0001) and diastolic BP (nicotine, 65.6 ± 6.4; control, 47.4 ± 3.1, p = 0.0003) at 10 min after starting injection of the loading dose; BP dropped to control levels in both groups at 30 min. During occlusion and reperfusion, the BP and heart rate were not altered by nicotine. Nicotine significantly increased myocardial infarct size as a percentage of the ischemic risk zone compared to the controls (nicotine, 54.9 ± 1.9; control, 48.6 ± 2.7, p < 0.05), but nicotine did not affect the no-reflow size and heart function. SignificanceWhile acute nicotine only transiently elevated blood pressure, it did not affect hemodynamic parameters during coronary artery occlusion. Nicotine increased myocardial infarct size, suggesting that the increase in infarct size was not simply due to an increase in oxygen demand due to altered afterload, heart rate, or contractility, but may have been due to a more direct effect on the myocardium.

Impact of Dexmedetomidine on Tourniquet-Induced Systemic Effects in Total Knee Arthroplasty under Spinal Anesthesia: a Prospective Randomized, Double-Blinded Study

Background Clinical studies on the impact of dexmedetomidine on tourniquet-induced systemic effects have been inconsistent. We investigated the impact of dexmedetomidine on tourniquet-induced systemic effects in total knee arthroplasty. Methods Eighty patients were randomly assigned to either control (CON) or dexmedetomidine (DEX) group. The DEX group received an intravenous loading dose of 0.5 μg/kg DEX over 10 minutes, followed by a continuous infusion of 0.5 μg/kg/h from 10 minutes before the start of surgery until completion. The CON group received the same calculated volume of normal saline. Pain outcomes and metabolic and coagulative changes after tourniquet application and after tourniquet release were investigated. Results The frequency of fentanyl administration postoperatively, patient-controlled analgesia (PCA) volume at 24 hours postoperatively, total PCA volume consumed in 48 hours postoperatively, and VAS score for pain at 24 and 48 hours postoperatively were significantly lower in the DEX group than in the CON group. Ten minutes after the tourniquet release, the DEX group showed significantly higher pH and lower lactate level than those in the CON group. Antithrombin III activity and body temperature 10 minutes after tourniquet release were significantly lower in the DEX group than in the CON group. Ca2+, K+, HCO3−, base excess, and PCO2 levels 10 minutes after tourniquet release were not significantly different between the two groups. Conclusion We showed that DEX attenuated pain and hemodynamic, metabolic, and coagulative effects induced by the tourniquet. However, these metabolic and coagulative changes were within normal limits. Therefore, DEX could be used as an analgesic adjuvant, but should not be considered for routine use to prevent the systemic effects induced by tourniquet use.