Intravenous Bolus Dose Research Articles

Continuous intravenous versus intermittent bolus midazolam with remifentanil during arteriovenous fistula placement with monitored anesthesia care in chronic renal failure patients: a randomized controlled trial.

ABSTRACTBACKGROUND: There is limited data on the use of intravenous continuous infusion (CI) versus intravenous intermittent bolus (IB) doses of midazolam for conscious sedation in patients with chronic renal failure. Unexpected adverse events can occur in chronic renal failure patients undergoing short procedures.OBJECTIVE: Investigate and compare the sedoanalgesic and adverse effects of intravenous continuous infusion (CI) use of midazolam with intravenous intermittent bolus (IB) doses of midazolam while using intravenous remifentanil as a rescue medication, and assess patient and surgeon satisfaction.DESIGN: Prospective, randomized, single-blind controlled study.SETTINGS: Two tertiary care hospitals.PATIENTS AND METHODS: Study included patients aged 43-81 years with a diagnosis of chronic renal failure who were referred for an arteriovenous fistula procedure with modified anesthesia care between August 2012 and April 2016. The patients were randomized to intravenous CI or IB doses of midazolam. IB doses of remifentanil were used as a rescue medication.MAIN OUTCOME MEASURES: Primary outcomes were amounts of midazolam and remifentanil medications during the operation, the amount of remifentanil as a rescue medication, and the satisfaction of patient and surgeon.SAMPLE SIZE: 116 assessed for eligibility; 99 randomized to CI (n=50) or IB doses (n=49 of midazolam).RESULTS: The total dose of midazolam by CI was greater than with midazolam by IB (P=.002). The total dose of remifentanil was higher with IB doses of midazolam in comparison to CI of midazolam (P=.001). The groups were similar in sedation and pain control, duration of procedure, recovery time, patient satisfaction and adverse events; surgeon satisfaction was greater with CI versus IB (P=.035).CONCLUSION: Intravenous CI midazolam during MAC provides better surgeon satisfaction then IB midazolam and can be used safely for arteriovenous fistula procedures.LIMITATIONS: Two different surgeon groups.CONFLICT OF INTEREST: None.

An UHPLC-TOF-MS method for quantifying novel brominated anticancer compound bromophenol-thiosemicarbazone hybrid and its application to in vivo pharmacokinetic study

BackgroundBromophenol-thiosemicarbazone hybrid was a novel synthetic brominated anticancer compound with two bromine atoms. Bromophenol-thiosemicarbazone hybrid showed considerable selective inhibitory activity against PARP1 (IC50 = 29.5 nmol/L). UHPLC-TOF-MS was used to establish a new method to quantify bromophenol-thiosemicarbazone hybrid bio-samples for indispensable quantitation analysis in further extensive pre-clinical studies.MethodsChromatographic and mass spectrometry parameters were optimized for quantitative method establishment. Improved protein-precipitated method was applied to the extraction of bromophenol-thiosemicarbazone hybrid in rat plasma samples. Furthermore, this proposed method was applied to an intravenous bolus dose to male rats.ResultsMobile phase was consisted of water for A and acetonitrile for B with 25 mmol/L formic acid in both A and B. The flow rate was 0.30 mL/min, and the run time of bromophenol-thiosemicarbazone hybrid was 4.0 min. A Thermo Fisher Accucore 2.6 μm C18 column (50 × 2.1 mm i.d.; San Jose, USA) was used for chromatographic separation. High resolution mass spectrometry was used to quantify samples by exact mass number of compound which was operated on negative ionization mode. Linear dynamic range of the established method was widely with 13.7–10000 nmol/L. Pharmacokinetics properties of bromophenol-thiosemicarbazone hybrid were shown in the results.ConclusionThis method was reliable and reproducible from sample preparation to analysis and storage stability under the investigated conditions. It may be useful for analysis of halogenated compounds and brominated compounds in ultra-performance liquid chromatography-mass spectrometry.

Pharmacokinetics of an intravenous bolus dose of clonidine in children undergoing surgery

Clonidine is used off-label in children but only limited pediatric pharmacokinetic data are available for intravenously administered clonidine. To determine pharmacokinetic parameter estimates of clonidine in healthy children undergoing surgery and to investigate age-related differences. Furthermore, to investigate possible pharmacokinetic differences of clonidine between this group of children and a cohort with cardiac diseases. In a randomized placebo-controlled trial (The PREVENT AGITATION trial), blood samples for clonidine pharmacokinetic analysis were collected in a proportion of the enrolled patients. Healthy children with ASA score 1-2 in the age-groups 1 to <2years and 2-5years were randomized for blood sampling. Clonidine was administered as a single intravenous bolus of 3µg/kg intraoperatively. Blood samples were drawn at baseline, 5, 10, 15, 30, 60minutes after dosing and additionally every hour until discharge from the PACU. Clonidine analysis was performed on liquid chromatography-mass spectrometry. Data form eighteen children were available for pharmacokinetic analysis (ASA I; male/female: 17/1; age: 1-5years; weight 8.7-24kg). Population parameter estimates for the 2-compartment model were similar to previous published data for children who underwent cardiac surgery. A pooled analysis including data from 59 children indicated clearance of 14.4Lh-1 70kg-1 and volume of distribution of 192.6L70kg-1 . No age-related pharmacokinetic differences and no difference in time from administration of study medication to awakening were found. Children 1 to <2years had a shorter PACU stay than children 2-5years (mean difference 17% 95% CI:3%-34%, P=.02). Pharmacokinetic parameter estimates were similar for children undergoing general surgery and cardiac surgery given a single dose of intravenous clonidine. These results indicated that no dose reduction is needed in children aged 1 to <2years compared with those 2-5years, which was supported by pharmacodynamic observations.

SUPPORT-1 (Subjects Undergoing PCI and Perioperative Reperfusion Treatment): A Prospective, Randomized Trial of CMX-2043 in Patients Undergoing Elective Percutaneous Coronary Intervention

The natural molecule α-lipoic acid has been shown to be partially cytoprotective through antioxidant and antiapoptotic mechanisms. To obtain an initial assessment of the safety and potential efficacy of a synthetic derivative, CMX-2043, in preventing ischemic complications of percutaneous coronary intervention (PCI) we conducted the Subjects Undergoing PCI and Perioperative Reperfusion Treatment (SUPPORT-1) trial, the first patient experience with this agent. SUPPORT-1 was a phase 2a, 6-center, international, placebo-controlled, randomized, double-blind trial. A total of 142 patients were randomized to receive a single intravenous bolus dose of drug or placebo administered 15-60 minutes before PCI. Cardiac biomarker assessments included serial measurements of creatine kinase myocardial band (CK-MB) at 6, 12, 18, and 24 hours after PCI and a single measurement of troponin T (TnT) at 24 hours. Peak concentrations of CK-MB and TnT were significantly reduced in the 2.4 mg/kg group compared with placebo (P = 0.05 and 0.03, respectively). No subject administered 2.4 mg/kg of CMX-2043 had an increase of CK-MB to ≥3X upper limit of normal versus 16% for placebo (P = 0.02); 16% of the 2.4-mg/kg dose group developed an elevation of TnT to ≥3X upper limit of normal versus 39% in the placebo group (P = 0.05). No drug-related serious adverse events were observed in any group. These data suggest that CMX-2043 may reduce PCI periprocedural myonecrosis and support further clinical evaluation of this novel agent for its potential cytoprotective effects.

Testing individual baroreflex responses to hypoxia-induced peripheral chemoreflex stimulation

IntroductionBaroreflexes and peripheral chemoreflexes control efferent autonomic activity making these reflexes treatment targets for arterial hypertension. The literature on their interaction is controversial, with suggestions that their individual and collective influence on blood pressure and heart rate regulation is variable. Therefore, we applied a study design that allows the elucidation of individual baroreflex–chemoreflex interactions.MethodsWe studied nine healthy young men who breathed either normal air (normoxia) or an air–nitrogen–carbon dioxide mixture with decreased oxygen content (hypoxia) for 90 min, with randomization to condition, followed by a 30-min recovery period and then exposure to the other condition for 90 min. Multiple intravenous phenylephrine bolus doses were applied per condition to determine phenylephrine pressor sensitivity as an estimate of baroreflex blood pressure buffering and cardiovagal baroreflex sensitivity (BRS).ResultsHypoxia reduced arterial oxygen saturation from 98.1 ± 0.4 to 81.0 ± 0.4% (p < 0.001), raised heart rate from 62.9 ± 2.1 to 76.0 ± 3.6 bpm (p < 0.001), but did not change systolic blood pressure (p = 0.182). Of the nine subjects, six had significantly lower BRS in hypoxia (p < 0.05), two showed a significantly decreased pressor response, and three showed a significantly increased pressor response to phenylephrine in hypoxia, likely through reduced baroreflex buffering (p < 0.05). On average, hypoxia decreased BRS by 6.4 ± 0.9 ms/mmHg (19.9 ± 2.0 vs. 14.12 ± 1.6 ms/mmHg; p < 0.001) but did not change the phenylephrine pressor response (p = 0.878).ConclusionWe applied an approach to assess individual baroreflex–chemoreflex interactions in human subjects. A subgroup exhibited significant impairments in baroreflex blood pressure buffering and BRS with peripheral chemoreflex activation. The methodology may have utility in elucidating individual pathophysiology and in targeting treatments modulating baroreflex or chemoreflex function.

The Effect of Midazolam and Dexmedetomidine Sedation on Block Characteristic Following Spinal Bupivacaine: A Randomized Comparative Study.

Background:Dexmedetomidine is widely used as an adjunct to general as well as regional anesthesia.Aims:This study was conducted to compare and evaluate the synergistic effect of single intravenous (i.v.) bolus dose of dexmedetomidine with midazolam on spinal block duration, analgesia, and sedation in patients undergoing infra-umbilical surgeries.Settings and Design:Prospective, randomized, comparative, and double-blinded study.Materials and Methods:One hundred patients between 18 and 60 years of age of American Society of Anesthesiologists physical status I and II posted for elective infra-umbilical surgery under subarachnoid block were randomly divided into two groups (Group D and Group M). Patients of Group D received i.v. dexmedetomidine 0.5 μg.kg−1 and of Group M received i.v. midazolam 0.05 mg.kg−1 as premedication 5 min before spinal anesthesia over 10 min. Vital parameters, Ramsay sedation score, level of sensory and motor block, recovery time for sensory blockade, postoperative numerical rating scale, time of requirement of the first dose of postoperative rescue analgesic, and duration of analgesia were recorded and analyzed.Statistical Analysis:Chi-square test, t-test, and analysis of variance test were applied to analyze data using SPSS package for Windows.Results and Conclusion:Premedication with single i.v. dexmedetomidine prolonged the duration and increased the maximum upper level of only sensory component of spinal anesthesia (6.42 ± 3.21 vs. 4.8 ± 1.21 thoracic segments higher than with midazolam sedation). This property can be beneficial in preventing undesirable prolongation of motor block and facilitating early ambulation in shorter duration of infra-umbilical surgeries. In addition, dexmedetomidine slowed the regression of sensory block and increased the time of the first request of analgesic.

Comparative study between preoperative ketamine bolus dose versus ketamine bolus plus infusion for perioperative analgesia in orthopedic surgery

Background and aim Postoperative pain severity depends on patient factors, anesthesia-related factors, and type of surgery. Pain after orthopedic surgery has been found to be immediate and severe, which necessitates more attention for its management. The aim of this study was assessment of the effectiveness of intravenous ketamine to provide postoperative analgesia after orthopedic surgery. This randomized double-blind study had been performed in Al-Zahraa University Hospital from December 2019 to October 2020. Patients and methods A total of 75 patients subjected to major orthopedic surgery were registered in the study. The patients had been randomly assigned into three equal groups (control, bolus, and bolus with infusion groups) to receive intravenous ketamine bolus dose alone (0.3 mg/kg) (bolus group); ketamine bolus (0.3 mg/kg) plus infusion (5 µg/kg/min), which terminated at the end of operation (bolus with infusion group); or placebo in the form of normal saline (control group). Visual analog pain scale score, postoperative 24 h morphine requirements, time to first analgesic requirement, and postoperative adverse effects were recorded and compared. Results Postoperative visual analog pain scale score and total morphine requirements were significantly less in bolus with infusion group, followed by bolus group, whereas the highest score and requirements were in control group. Regarding the time to first analgesic requirement, there was a statistically significant increased time to first analgesic in bolus with infusion group, followed by bolus group, whereas the shortest time was in control group, and there were nonsignificant differences among groups regarding postoperative complications. Conclusion Ketamine bolus dose alone before skin incision or followed by infusion had the capability of decreasing postoperative pain and total analgesic requirement and increasing the time to first analgesic requirement after orthopedic surgery, with superiority of ketamine bolus dose plus infusion without increasing the incidence of adverse effects.

Methylene blue? Therapeutic Alternative in the Management of Septic Shock Refractory to Norepnephrine

Introduction: Methylene blue is receiving special interest in perioperative and intensive care of patients with distributive shock due to its ability to block the action of nitric oxide and to antagonize deep vasodilation. Objective: The objective is to illustrate the use of the methylene blue, summarizing the perioperative management of a case with secondary vasoplegic syndrome due to a norepinephrine refractory septic shock and the response to methylene blue, reviewing the latest evidence of this therapeutic alternative. In practice:We describe the case of a 60-year-old man, paraplegic, with septic shock due to a long evolution decubitus pressure ulcer. After two hours of surgery, the patient remained with hemodynamic deterioration despite high doses of vasopressin (3 IU/hour) and norepinephrine (2 µg/kg /min), therefore methylene blue was administered with two intravenous bolus doses of 50 mg without adverse effects. After half an hour hemodynamic improvement was evidenced, allowing to decrease norepinephrine infusion and normalizing blood pressure. Finally, debridement of necrotic tissue, amputation and disarticulation of left coxofemoral joint was performed with subsequent transfer to the ICU and discharge to the spinal cord injury ward twenty eight days later. Conclusions: As it has been demonstrated in our patient, methylene blue is a therapeutic alternative to manage patients with persistent hypotension despite the use of various vasopressors during the management of vasoplegic syndrome secondary to septic shock.

Attenuation of hemodynamic response to laryngoscopy and tracheal intubation in adult patients with a single intravenous bolus dose of dexmedetomidine - A prospective, randomized, double-blind, controlled clinical study

Background: Performing laryngoscopy and endotracheal intubation evokes a reflex circulatory response, which results in an increase in the blood pressure and heart rate (HR) and causes arrhythmia due to increased outflow from the sympatho-adrenal axis. Aim and Objective: The aim of this study was to evaluate the efficacy of a single bolus dose of 0.6 mg/kg body weight dexmedetomidine, a centrally acting α-2 agonist, through intravenous route, in attenuating the hemodynamic responses to laryngoscopy and endotracheal intubation. Materials and Methods: It was a randomized, prospective, two fold-blinded, and placebo-controlled clinical study. After obtaining Ethical Committee clearance, 100 adult patients in the age group of 18–50 years were enrolled. Blood pressure of the patients enrolled was within the normal range and they were posted for various elective surgeries. Categorization was performed with the American Society of Anaesthesiologists and Mallampatti as Class I and II Grade I and II, respectively. The patients were randomly distributed into two groups, Group A and Group B. Group A included 50 patients (n = 50) and was treated with 1 ml/kg of normal saline intravenously for about 10 min and 10 min before the induction. Group B included 50 patients (n = 50) and was treated with dexmedetomidine 1 ml/kg (0.6 μg/kg body weight), which was further diluted in 100 ml ordinary saline and given intravenously, for about 10 min and 10 min before the induction. After premedication, anesthesia was induced with injection thiopentone 5 mg/kg body weight and was given until the loss of eyelash reflex. Dose of thiopentone required was noted. It was followed by injection succinylcholine 1.5 mg/kg body weight. HR, systolic blood pressure (SBP), diastolic blood pressure (DBP), and mean arterial pressure (MAP) were the various parameters for analysis and recorded at regular time intervals. Results: Initiation of laryngoscopy and intubation resulted in significant rise in the HR (36.14 bpm), SBP (29.22 mmHg), DBP (20.30 mmHg), and MAP (14.46 mmHg) in patients who were grouped under Group A. In Group B (dexmedetomidine), mean of HR, SBP, DBP, and MAP decreased by 2.86 bpm, 17.66 mmHg, 1.54 mmHg, and 4.98 mmHg, respectively, when compared to basal values which is statistically highly significant (P < 0.0001). Conclusion: Dexmedetomidine, at the dose of 0.6 μg/kg body weight when given intravenously 10 min before induction was noted to efficiently reduce the hemodynamic response to laryngoscopy and tracheal intubation.

Prophylactic co-administration of two different bolus doses of norepinephrine in spinal-induced hypotension during caesarean section: A prospective randomized double-blinded study

Background: Vasopressors for prophylaxis and treatment of spinal hypotension have grown in popularity in recent years. Norepinephrine is now emerging as one of the feasible options for prevention as well as management of spinal-induced hypotension in caesarean section (CS). The aim of our study was to compare the efficacy of two different doses of norepinephrine as prophylaxis for spinal-induced hypotension during CS. Material and Methods: Total 110 patients were recruited in this prospective randomized double-blind study from December 2017 to June 2019. After fulfilling the inclusion and exclusion criteria, this study was conducted on 90 patients undergoing elective CS under spinal anesthesia, who were assigned into three groups of 30 patients each. Group N6received norepinephrine 6 μg as an intravenous bolus, group N4received norepinephrine 4 μg, and group C received normal saline simultaneously with subarachnoid block. Incidence of hypotension, requirement of rescue doses of norepinephrine, time of first rescue dose, hemodynamic parameters, adverse effects, and neonatal complications were assessed, compared and analyzed. Results: The incidence of post spinal hypotension was 63.33% in group N6, 80% in group N4, and 83.33% in group C (p = 0.155). Total rescue dose requirement of norepinephrine was significantly less in group N6(8.21 ± 2.97 μg) as compared to N4(9.00 ± 3.06 μg) and control group (11.00 ± 4.57 μg).(p = 0.011). The median time to first rescue dose requirement of norepinephrine was significantly delayed in group N6(6[8–4.5] min) and group N4(4[9–2.5] min) as compared to control group (4[5–2] min) (p = 0.004). Conclusion: Prophylactic intravenous bolus dose of 6 μg norepinephrine when co-administered with spinal anesthesia was found to be more effective than 4 μg norepinephrine in terms of decreasing total rescue dose requirement of vasopressor and delaying the time to first rescue dose, without significant change in the incidence of hypotension.

Uterotonics in Elective Caesarean Delivery: A Randomised Noninferiority Study Comparing Carbetocin 20 and 100 µg

(Anaesthesia. 2019;74:190–196) Postpartum hemorrhage (PPH) is the most common cause of maternal mortality worldwide and accounts for 35% of maternal deaths. Active management of the third stage of labor is recommended in all parturients, with prophylactic uterotonic drug administration after delivery of the infant being the primary component of this active management. This strategy alone has been shown to decrease the incidence of PPH by up to 40%. The 2009 guidelines from the Society of Obstetricians and Gynaecologists of Canada (SOGC) recommended a single 100 µg intravenous bolus dose of carbetocin as the uterotonic agent of choice, rather than an oxytocin infusion, to prevent PPH after elective cesarean delivery. The rationale for recommending this dose was based on the manufacturer’s recommendation and some clinical trials. Some more recent studies, however, have suggested that doses as low as 15 µg may be effective at preventing PPH after elective cesarean delivery. The current investigators believed a larger trial comparing this smaller dose with the standard 100 µg dose was warranted to confirm these findings. This study was undertaken to compare the uterine tone intensity achieved with 20 carbetocin versus 100 µg carbetocin in women at low risk of PPH undergoing elective cesarean delivery under spinal anesthesia.

Contrast Enhanced Ultrasound Detects Endoleak after EVAR

Introduction - The major complications of endovascular aneurysm repair (EVAR) for abdominal aortic aneurysms (AAA) include endoleak, stentgraft migration and increased aneurysm sac size with subsequent risk of rupture. Thus, EVAR requires lifetime follow-up. Contrast-enhanced computed tomographic angiography (CTA) is considered the gold standard in follow-up after EVAR. However, repeat CTA is potentially harmful due to accumulated radiation1; and the association between contrast agents and reduced renal function. Contrast agents used in contrast-enhanced ultrasound (CEUS) are not nephrotoxic and CEUS has been reported to be able to detect endoleak after EVAR2. The aim of this study was to investigate the preciseness of CEUS vs CTA in follow-up after EVAR. Methods - Ninety-two patients (79 men) operated with EVAR for AAA between Jan 2013 and May 2016 was prospectively, consecutively enrolled. Mean age was 74 years (range 57 – 92). Follow-up was done with CTA and CEUS at one, six, 12 and 24 months. At each follow-up, CTA and CEUS were done the same day. The results from CTA were blinded from the operator doing CEUS and vice versa. A GE Logiq E9 ultrasound machine and an abdominal curvilinear 2-5MHz probe were used for the CEUS. The ultrasound contrast agent used in this study was SonoVue® (2.4ml dispersion intravenous bolus dose). The presence of endoleak was registered as a dichotomous variable and CTA was defined as the gold standard. Statistical analyses were done using crosstabs and chi-square tests (IBM, SPSS Statistics v24). Results - 236 paired CEUS and CTA were performed. In total, 48 endoleaks were documented on CTA. The overall sensitivity of CEUS was 89 % and the specificity 100 %. The number of endoleaks detected at one, six, 12 and 24 months postoperatively are listed in Table 1. At six months, five new endoleaks were found on CTA and two with CEUS. At 12 and 24 months, no new cases of endoleak were detected by either modality. In all four cases of endoleak detected on CTA but missed on CEUS, poor visualization on CEUS due to high body mass index (median 30.5) was reported. All cases of endoleaks were type 2.Table 1Number of patients with paired CTA and CEUS performed during follow-up and the sensitivity and specificity of endoleak detection by CEUSFollow-up, monthsPatients (n)Endoleaks on CEUS vs CTASensitivity (%)Specificity (%)17311/129210066813/1776100126312/1210010024326/6100100 Open table in a new tab Conclusion - In the present study, CEUS showed high sensitivity and specificity for detecting endoleak. CEUS may replace CTA in most patients during follow-up after EVAR.

Formulation of acyclovir-loaded solid lipid nanoparticles: 2. Brain targeting and pharmacokinetic study

Acyclovir (ACV) is widely used in the treatment of herpes encephalitis. The present study was conducted to prepare chitosan-tween 80 coated solid lipid nanoparticles (SLNs) as a delivery system for brain targeting of ACV in rabbits. The SLNs were prepared and coated in one step by microemulsion method using a coating solution containing chitosan (0.1% w/v) and tween 80 (2% w/v) for loading sustained release ACV. In vitro characterization was performed for coated ACV-SLNs. Concerning in vivo experiments; a single intravenous bolus dose of coated ACV-SLNs was given versus free ACV solution to rabbits (62 mg/kg). Plasma pharmacokinetic parameters were calculated from the ACV concentration-time profiles in plasma using the two compartmental analysis. The values of AUC0−∞ and MRT of coated ACV-SLNs were higher than free drug by about twofold, 233.36 ± 41.56 μg.h/mL and 1.81 ± 0.36 h, respectively. The noncompartmental analysis was conducted to estimate the brain pharmacokinetic parameters. The AUC0−∞ brain/AUC0−∞ plasma ratio for coated ACV-SLNs and free ACV was 0.22 and 0.12, respectively. These results indicated the effectiveness of using coated ACV-SLNs for brain targeting.

A prospective, randomized clinical trial for comparison of pethidine and dexmedetomidine for the control of intraoperative shivering under spinal anaesthesia

Introduction: Pharmacological methods using variety of drugs like pethidine, morhine, tramadol, clonidine, doxapram, ketansarine, nefopam, neostigmine, magnesium sulfate have been tried in post spinal shivering. Aim of the present study was to compare the two drugs pethidine and dexmedetomidine for the control of intraoperative shivering under spinal anaesthesia. Materials and Methods: A prospective randomized study where total 80 patients of either gender aged between 20-60 years, ASA grade of I -II and patients who develop shivering of grade 2-3 (Crossley and Mahajan scale) after spinal anaesthesia were enclosed within the study after getting informed consent. The patients were randomized into two groups of 40 patients each. Group D- Dexmedetomidine group received single intravenous bolus dose of dexmeditomidine 0.5mcg/kg over 5 min. Group P -Pethidine group patients received 0.5mg/kg Pethidine IV over 5 min. The time was accurately noted in seconds from drug administration to the disappearance of shivering. Patients were monitored at intervals of 1 minute, 3min, 5min and thenceforth 10, 20 and 30 minutes until finish of surgery. Patients were intently monitored for failure of the drug, recurrence of shivering and side effects such as nausea, vomiting, bradycardia (20% of baseline), giddiness and sedation score will be recorded. Chi-square test was accustomed to evaluate categorical factors. Results: Dexmedetomidine group had significant reduction in time needed to control shivering and disappearance of shivering after drug administration. Conclusion: Through this study we tend to found that the time taken for control of shivering was shorter with Dexmedetomidine as compared to Pethidine. Side effects were less with Dexmedetomidine as compared to Pethidine. Keywords: Pethidine, Dexmedetomidine, Spinal anaesthesia, Shivering.

Microdialysis combined with liquid chromatography-tandem mass spectrometry for the quantitation of gemifloxacin and its application to a muscle penetration study in healthy and MRSA-infected rats.

Pharmacological efficacy is based on the drug concentration in target tissues, which usually cannot be represented by the plasma concentration. The purpose of this study was to compare the pharmacokinetic characteristics of gemifloxacin in plasma and skeletal muscle and evaluate its tissue penetration in both healthy and MRSA (methicillin-resistant Staphylococcus aureus)-infected rats. A microdialysis (MD) combined with liquid chromatography-tandem mass spectrometry (LC-MS/MS) method was developed and validated to determine free gemifloxacin concentrations in rat plasma and skeletal muscle simultaneously. The in vivo recoveries of MD were 23.21% ± 3.42% for skeletal muscle and 20.62% ± 3.19% for plasma, and were concentration independent. We provided evidence that the method developed here meets FDA requirements. Additionally, this method was successfully applied to the determination of free gemifloxacin in rats. Muscle and blood dialysates were collected after an 18 mg/kg intravenous bolus dose. The mean areas under the concentration-time curves (AUCs) from 0 to 9 h for skeletal muscle and plasma were 3641.50 ± 915.65 h*ng/mL and 7068.32 ± 1964.19 h*ng/mL in MRSA-infected rats and 3774.72 ± 700.36 h*ng/mL and 6927.49 ± 1714.86 h*ng/mL in healthy rats, respectively. There was no significant difference (P>0.05) in gemifloxacin exposure between healthy rats and MRSA-infected rats for plasma or muscle. The low ratio of AUC0-9 muscle to AUC0-9 plasma suggested lower drug exposure in skeletal muscle than in plasma for both healthy and MRSA-infected rats. Our study suggested that the administration of gemifloxacin according to drug levels in plasma to treat local infection is unreasonable and might result in an inadequate dose regimen.

Near Infrared Spectroscopy Based Clinical Algorithm Applicability During Spinal Neurosurgery and Postoperative Cognitive Disturbances.

Background and Objectives: Postoperative cognitive disturbances (POCD) can significantly alter postoperative recovery. Inadequate intraoperative cerebral oxygen supply is one of the inciting causes of POCD. Near-infrared spectroscopy (NIRS) devices monitor cerebral oxygen saturation continuously and can help to guide intraoperative patient management. The aim of the study was to evaluate the applicability of the NIRS-based clinical algorithm during spinal neurosurgery and to find out whether it can influence postoperative cognitive performance. Materials and Methods: Thirty four patients scheduled for spinal neurosurgery were randomized into a study group (n = 23) and a control group (n = 11). We monitored regional cerebral oxygen saturation (rScO2) throughout surgery, using a NIRS device (INVOS 4100). If rScO2 dropped bilaterally or unilaterally by more than 20% from baseline values, or under an absolute value of 50%, the NIRS-based algorithm was initiated in the study group. In the control group, rScO2 was monitored blindly. To evaluate cognitive function, Montreal-Cognitive Assessment (MoCA) scale was used in both groups before and after the surgery. Results: In the study group, rScO2 dropped below the threshold in three patients and the NIRS-based algorithm was activated. Firstly, we verified correct positioning of the head; secondly, we increased mean systemic arterial pressure in the three patients by injecting repeated intravenous bolus doses of Ephedrine, ultimately resulting in an rScO2 increase above the approved threshold level. None of the three patients showed POCD. In the control group, one patient showed a drop in rScO2 of 34% from baseline and presented with a POCD. RScO2 drop occurred with other stable intraoperative measurements. Conclusions: A significant rScO2 drop may occur during spinal surgery in prone position despite other intraoperative measurements remaining stable, allowing it to stay otherwise unrecognized. Use of the NIRS-based clinical algorithm can help to avoid POCD in patients after spinal surgery.

A clinical study investigation the three months prognosis of patients with ischemic stroke treated with recombinant tissue plasminogen activator (rtPA) and its effective factors

Objective: Currently, treating ischemic stroke by intravenous thrombolytic therapy has acceptable results in patients with stroke. This study aimed to evaluate the three months prognosis of patients treated with recombinant tissue plasminogen activator (rt-PA). Methods: This cross-sectional prospective study was conducted on 30 patients with cerebral ischemic stroke with the National Institutes of Health Stroke Scale (NIHSS) &gt;5. Data such as demographic information, signs and symptoms, medical history, risk factors, focused neurological examination, and the NIHSS were collected for all patients. Then, all patients received 0.9 mg/kg of rt-PA as intravenous bolus doses and intravenous infusion under close monitoring in the emergency department. All patients were checked for necessary outcomes and also disability at the admission time, 7 days later and after three months all patients were checked again. All collected data were analyzed by appropriate tests using SPSS version 22. Results: Of all patients, 63.3% were males and 36.7% were females. The mean age of the patients was 62.37 ± 12.62 years with a range of 40-91 years. The mean of NIHSS was 12.46 ± 4.28 at admission time, in day seven it was 8.06 ± 3.72 and in month three after treatment it was 3.62 ± 2.31. There was a significant relationship between age, place of residence and NIHSS. Thirty percent of patients had NIHSS more than 15 at admission time and after 7 days this rate reached to 10% and three months later it declined to 6.7%. These differences were statistically significant. Conclusion: Intravenous thrombolytic therapy is associated with proper short term results in most patients with ischemic stroke.

Prevention of chronic kidney disease progression in patients with acute decompensation of chronic heart failure

Aim.To assess the efficiency of the program of prevention of chronic kidney disease (CKD) progression in patients with acute decompensation of chronic heart failure (CHF). The program included the use of nitrendipine, a calcium channel antagonist, and the replacement of single intravenous bolus dosing of furosemide with a prolonged intravenous infusion in the early stage of the disease.Material and methods.One hundred twenty five patients with decompensation of CHF were examined and divided into 2 groups. Group 1 received standard therapy. In the group 2, an additional prevention program was carried out. The criterion of CKD progression was the change in glomerular filtration rate (GFR) in accordance with the KDIGO guidelines (2012). GFR was calculated by two methods: serum creatinine and cystatin C levels. The parameters were monitored and compared with baseline levels at admission to the hospital and on the 10th day of therapy. For the initial level was taken the patient’s GFR, calculated by the serum creatinine level prior to the present hospitalization on the background of a satisfactory condition.Results.At admission to the hospital, in group 1 CKD progression was established in 33,3% of patients, in group 2 — in 29,3%. On the 10th day, CKD progression was noted in 47,4% of patients in group 1, in group 2 — in 23,4%.Conclusion.The prevention program allows to reduce the number of cases of CKD progression in patients with decompensation of CHF by 2 times.

Physiologically based pharmacokinetic modelling to predict exposure differences in healthy volunteers and subjects with renal impairment: Ceftazidime case study.

Ceftazidime is a widely used β-lactam antibiotic and almost entirely excreted via glomerular filtration in kidney. The objective of this analysis was to assess the ability of physiologically based pharmacokinetic (PBPK) model to predict ceftazidime exposure in healthy volunteers and subjects with renal impairment. A full PBPK model of ceftazidime was developed using physiochemical properties and clinical data. The total clearance of 115mL/min and renal clearance of 100mL/min were obtained from ceftazidime package insert. Healthy and chronic kidney disease (CKD) populations were applied for sampling of virtual subjects. The established PBPK model predicted mean plasma AUCinf were 138.5±19.6, 230.7±22.2, 369.3±53.1 and 561.8±92.4hµg/mL in healthy, mild, moderate and severe renal impairment subjects, respectively, after administration of 1g ceftazidime intravenous bolus dose. The predicted values were in close agreement with the weighted mean of the five reported clinical studies. The exposure was slightly under predicted in subjects with severely impaired renal function, but still within 1.5-fold range. The concentration-time profiles of ceftazidime were also well captured in healthy volunteers and subjects with renal impairment. The developed PBPK model along with systems pharmacokinetics (PK) (renal impaired populations) well predicted the ceftazidime exposure. PBPK models verified with clinical study in healthy volunteers could be potentially applied to predict PK and recommend dose adjustment for CKD patients.

Attenuation of haemodynamic responses of laryngoscopy and endotracheal intubation: An evaluation of efficacy of single intravenous dose of esmolol hydrochloride

Attenuation of haemodynamic responses of laryngoscopy and endotracheal intubation: An evaluation of efficacy of single intravenous dose of esmolol hydrochloride - IJCA- Print ISSN No: - 2394-4781 Online ISSN No:- 2394-4994 Article DOI No:- 10.18231/2394-4994.2019.0009, Indian Journal of Clinical Anaesthesia-Indian J Cl