Initial Bolus Research Articles

Effects of acepromazine, xylazine and propofol on spinal reflexes in healthy dogs.

In the neurological examination, it is crucial to identify the possible location of the lesion in order to determine the appropriate treatment process. In aggressive animals, chemical restraint may be necessary due to their non-cooperative behaviour. However, sedatives may distort the results of examinations. Therefore, a drug should be found that has minimal impact on the examination results. To investigate the effects of acepromazine, xylazine, and propofol on spinal reflexes in healthy dogs. In a randomized, blinded study, ten native adult mixed-breed dogs were participated in three groups with a 1-week washout period between each group. Before performing each step, the spinal reflexes were evaluated. Then, in the first group, acepromazine (0.05mg/kg, IM), in the second group, xylazine (1mg/kg, IM), and in the third group, propofol (3mg/kg, IV for initial bolus and 0.1mg/kg/min for maintenance) were injected for sedation. The spinal reflexes were reevaluated at maximum sedation and at 15, 30, and 45 min thereafter. Acepromazine increased the patellar reflex and decreased the panniculus reflex. Xylazine increased the cranial tibial reflex and decreased the panniculus reflex, while propofol decreased the withdrawal, and extensor carpi radialis reflexes, and suppressed the palpebral and gag reflexes. The drugs used in the present study did not have a significant impact on the most important reflexes evaluated in neurological examinations. Among the drugs, acepromazine has the least effects compared to other drugs, making it a suitable choice for sedation.

Preliminary Exploration of Variations in Measures of Pharyngeal Area During Nonswallowing Tasks.

Age- and disease-related changes in oropharyngeal anatomy and physiology may be identified through quantitative videofluoroscopic measures of pharyngeal area and dynamics. Pixel-based measures of nonconstricted pharyngeal area (PhAR) are typically taken during oral bolus hold tasks or on postswallow rest frames. A recent study in 87 healthy adults reported mean postswallow PhAR of 62%(C2-4)2, (range: 25%-135%), and significantly larger PhAR in males. The fact that measures were taken after initial bolus swallows without controlling for the presence of subsequent clearing swallows was identified as a potential source of variation. A subset of study participants had completed a protocol including additional static nonswallowing tasks, enabling us to explore variability across those tasks, taking sex differences into account. Videofluoroscopy still shots were analyzed for 20 healthy adults (10 males, 10 females, Mage = 26 years) in head-neutral position, chin-down and chin-up positions, a sustained /a/ vowel vocalization, and oral bolus hold tasks (1-cc, 5-cc). Trained raters used ImageJ software to measure PhAR in %(C2-4)2 units. Measures were compared to previously reported mean postswallow PhAR for the same participants: (a) explorations of sex differences; (b) pairwise linear mixed-model analyses of variance (ANOVAs) of PhAR for each nonswallowing task versus postswallow measures, controlling for sex; and (c) a combined mixed-model ANOVA to confirm comparability of the subset of tasks showing no significant differences from postswallow measures in Step 2. Overall, PhAR measures were significantly larger in male participants; however, most pairwise task comparisons did not differ by sex. No significant differences from postswallow measures were seen for 5-cc bolus hold, chin-down and chin-up postures, and the second (but not the first) of two repeated head neutral still shots. PhAR during a 5-cc bolus hold was most similar to postswallow measures: mean ± standard deviation of 51 ± 13%(C2-4)2 in females and 64 ± 16%(C2-4)2 in males. PhAR is larger in men than in women. Oral bolus hold tasks with a 5-cc liquid bolus yield similar measures to those obtained from postswallow rest frames.

Successful Use of Propofol After Failed Palliative Sedation in Patients With Refractory Symptoms.

Context: Propofol is a general anesthetic used in multiple clinical scenarios. Despite growing evidence supporting its use in palliative care, propofol is rarely used in palliative sedation. Reluctance toward the adoption of propofol as a sedative agent is often associated with fear of adverse events such as respiratory arrest. Objectives: We aimed to describe efficacy and safety of palliative sedation in refractory sedation with propofol using a protocol based on low, incremental dosing. Methods: A retrospective observational study featuring inpatients receiving sedative treatment with propofol in our palliative care unit in Madrid (Spain) between March 1, 2018 and February 28, 2023, following a newly developed protocol. Results: During the study period, 22 patients underwent sedation with propofol. Propofol was used successfully to control different refractory symptoms, mainly psychoexistential suffering and delirium. All patients had undergone previous failed attempts at sedation with other medications (midazolam or lemovepromazine) and presented risk factors for complicated sedation. All patients achieved satisfactory (profound) levels of sedation measured with the Ramsay Sedation Scale, but total doses varied greatly between patients. Most patients (17, 77%) received combined therapy with propofol and other sedative medications to harness synergies. The median time between start of sedation with propofol and death was 26.0 hours. No cases of apnea or death during induction were recorded. Conclusion: A protocol for palliative sedation with propofol based on low, incremental dosing, with the option of administering an initial induction bolus, shows excellent results regarding adequate levels of sedation, without observing apnea or respiratory depression. Our results promote the use of propofol to achieve palliative sedation in patients with refractory symptoms and risk factors for complicated sedation at the end of life.

Haptoglobin Administration for Intravascular Hemolysis: A Systematic Review.

Exogenous haptoglobin administration may enhance plasma-free hemoglobin (pfHb) clearance during hemolysis and reduce its end-organ damage: we systematically reviewed and summarized available evidence on the use of haptoglobin as a treatment for hemolysis of any cause. We included studies describing haptoglobin administration as treatment or prevention of hemolysis-related complications. Only studies with a control group reporting at least one of the outcomes of interest were included in the quantitative synthesis. Primary outcome was the change in pfHb concentration 1 h after haptoglobin infusion. Among 573 articles, 13 studies were included in the review (677 patients, 52.8% received haptoglobin). Median initial haptoglobin intravenous bolus was 4,000 (2,000, 4,000) IU. Haptoglobin was associated with lower pfHb 1 h (SMD -11.28; 95% CI: -15.80 to -6.75; p < 0.001) and 24 h (SMD -2.65; 95% CI: -4.73 to -0.57; p = 0.001) after infusion. There was no difference in all-cause mortality between haptoglobin-treated patients and control group (OR 1.41; 95% CI: 0.49-4.95; p = 0.520). Haptoglobin was associated with a lower incidence of acute kidney injury (OR 0.64; 95% CI: 0.44-0.93; p = 0.020). No adverse events or side effects associated with haptoglobin use were reported. Haptoglobin administration has been used in patients with hemolysis from any cause to treat or prevent hemolysis-associated adverse events. Haptoglobin may reduce levels of pfHb and preserve kidney function without increase in adverse events.

Intravenous initial bolus during prophylactic norepinephrine infusion to prevent spinal hypotension for cesarean delivery: A randomized controlled, dose-finding trial

BackgroundPrevious studies have shown that a 0.05 μg/kg/min of norepinephrine infusion in combination with an initial bolus reduces the incidence of spinal hypotension during cesarean delivery. The initial norepinephrine bolus influences the incidence of spinal hypotension during continuous norepinephrine infusion; however, the ideal initial bolus dose for 0.05 μg/kg/min of continuous infusion remains unknown. MethodsThis randomized, controlled, dose-finding study randomly allocated 120 parturients scheduled for elective cesarean delivery to receive initial bolus doses of 0, 0.05, 0.10, and 0.15 μg/kg of norepinephrine, followed by continuous infusion at a rate of 0.05 μg/kg/min. The primary outcome was the dose-response relationship of the initial norepinephrine bolus in preventing the incidence of spinal hypotension. Spinal hypotension was defined as systolic blood pressure (SBP) decreased to <80% of the baseline value or to an absolute value of <90 mmHg from intrathecal injection to delivery, and severe spinal hypotension was defined as SBP decreased to <60% of the baseline value. The secondary outcomes included the incidence of nausea and/or vomiting, hypertension, and bradycardia, as well as the Apgar scores and results of the umbilical arterial blood gas analysis. The effective dose (ED) 90 and ED95 were estimated using probit regression. ResultsThe per-protocol analysis included 117 patients. The incidence of spinal hypotension varied significantly among the groups: Group 0 (51.7%), Group 0.05 (44.8%), Group 0.10 (23.3%), and Group 0.15 (6.9%). The ED90 and ED95 values were 0.150 μg/kg (95% confidence interval [CI], 0.114–0.241 μg/kg) and 0.187 μg/kg (95% CI, 0.141–0.313 μg/kg), respectively. However, the ED95 value fell outside the dose range examined in this study. The incidence of severe spinal hypotension differed significantly (P = 0.02) among Groups 0 (17.2%), 0.05 (10.3%), 0.10 (3.3%), and 0.15 (0.0%); however, the incidence of hypertension and bradycardia did not. The incidence of nausea and/or vomiting decreased with an increase in the initial bolus dose (P = 0.03). The fetal outcomes were comparable among the groups. ConclusionsAn initial bolus of 0.150 μg/kg of norepinephrine may be the optimal dose for preventing spinal hypotension during cesarean delivery with a continuous infusion rate of 0.05 μg/kg/min, and does not significantly increase the incidence of hypertension but substantially reduces the risk of nausea and/or vomiting.

Thiamylal serum concentration for refractory convulsive status epilepticus while associated decreased concentrations of concomitant antiepileptics: a case report

BackgroundTreating refractory status epilepticus (RSE) remains a challenge. Thiamylal can be used as a second- or third-line treatment; however, its potential to induce cytochrome P450 (CYP) activity may reduce the concentration of antiepileptic drugs (AEDs) administered prior to thiamylal. This report details a case of RSE patient treated with thiamylal, with monitored concentrations of thiamylal and other AEDs.Case presentationA 72-year-old healthy man developed RSE. Despite the administration of various AEDs, his seizures were not resolved. Thiamylal was then administered at an initial bolus dose of 2.1 mg/kg, followed by a continuous infusion of 4.2–5.2 mg/kg/h. The initial thiamylal concentration was observed at 7.8 μg/mL, increasing to 35.2 μg/mL before decreasing after dose reduction and cessation. Concurrently, the concentration of concomitant carbamazepine decreased from 5.59 μg/mL to 2.1 μg/mL and recovered as thiamylal concentration decreased. Lesser impacts were noted for other AEDs.ConclusionsThis case report underscored the efficacy of thiamylal in treating RSE. However, it also highlighted the need for clinicians to closely monitor the concentrations of concurrent AEDs, especially carbamazepine, during thiamylal therapy.

Ketamine reduces seizure and interictal continuum activity in refractory status epilepticus: a multicenter in-person and teleneurocritical care study.

There is not a preferred medication for treating refractory status epilepticus (RSE) and intravenous ketamine is increasingly used. Ketamine efficacy, safety, dosage, and influence of other variables on seizure cessation while on ketamine infusions are not well studied. We aimed to characterize ketamine effect on RSE, including interictal activity on electroencephalogram (EEG) and when done by Teleneurocritical care (TNCC). We conducted a multicenter, retrospective study from August 2017 to October 2022. Patients 18years or older who had RSE and received ketamine were included. The primary outcome was effect of ketamine on RSE including interictal activity; secondary outcomes were effect of other variables on RSE, care by TNCC, ketamine infusion dynamics, adverse events, and discharge outcomes. Logistic regression was used. Fifty-one patients from five hospitals met inclusion criteria; 30 patients had RSE and interictal activity on EEG. Median age was 56.8years (IQR 18.2) and 26% had previously diagnosed epilepsy. Sixteen (31%) patients were treated virtually by TNCC. In those with RSE on EEG, ketamine was added as the fourth antiseizure medication (mean 4.4, SD 1.6). An initial bolus of ketamine was used in 24% of patients (95mg, IQR 47.5), the median infusion rate was 30.8 mcg/kg/min (IQR 40.4), and median infusion duration was 40h (IQR 37). Ketamine was associated with 50% cessation of RSE and interictal activity at 24h in 84% of patients, and complete seizure cessation in 43% of patients. In linear regression, ASMs prior to ketamine were associated with seizure cessation (OR 2.6, 95% CI 0.9-6.9, p = 0.05), while the inverse was seen with propofol infusions (OR 0.02, 95% CI 0.001-0.43, p = 0.01). RSE management by in-person NCC versus virtual by TNCC did not affect rates of seizure cessation. Ketamine infusions for RSE were associated with reduced seizure burden at 24h, with 84% of patients having 50% seizure reduction. Similar efficacy and safety was observed irrespective of underlying RSE etiology or when done via TNCC vs in-person NCC.

Recognizing Complications in Youth With Diabetes Admitted With Diabetic Ketoacidosis Versus Hyperglycemic Hyperosmolar State

IntroductionAlthough the numbers of youth with diabetes mellitus (DM) who have diabetic ketoacidosis (DKA) and hyperglycemic hyperosmolar state (HHS) are increasing, data regarding acute complications are limited. We compare in-hospital complications in youth with isolated DKA to those in youth with hyperosmolarity. MethodsWe reviewed medical records of youth (ages 1-20 years) admitted over a two-year period with DKA (serum bicarbonate ≤16 mEq/L; ketones ≥0.6 mmol/L), HHS (blood glucose ≥33.3 mmol/L [600 mg/dL]; osmolality ≥320 mOsm/kg), and hyperosmolar DKA. We evaluated outcomes including hospital length of stay (LOS), altered mental status (AMS), and acute kidney injury (AKI). ResultsOf 369 admissions, 334 (90.5%) had isolated DKA, 32 (8.7%) had hyperosmolar DKA, and three (0.8%) had isolated HHS. Compared to youth with isolated DKA, hyperosmolar youth had longer LOS (median 37.4 hours [IQR=24.6,63.5] vs 26.5 hours [IQR=20.2,41.3], p=0.002) and larger initial fluid boluses (median 10.28 ml/kg [IQR=10.00,19.75] vs 10.02 ml/kg [9.96,10.55], p=0.013). Hyperosmolar youth also had more frequent pediatric intensive care unit admission (71% vs 28%, p<0.001), AKI (63% vs 15%, p<0.001), and AMS (46% vs 12%, p<0.001). Multivariable logistic regression indicated the odds of AKI were positively associated with serum osmolality (OR 1.11; 95% CI 1.08-1.14; p<0.001) and negatively associated with new-onset DM compared to established DM (OR 0.32; 95% CI, 0.14-0.71; p=0.005). ConclusionIn youth with DM, hyperosmolarity increases acute complications compared to isolated DKA. Larger-scale studies are needed. Our findings can guide interventional studies and identify ways to prevent acute complications in youth experiencing hyperglycemic emergencies.

Cross-sectional investigation of activated clotting time after administration of different intravenous heparin doses in patients undergoing on-pump coronary artery bypass graft surgery

IntroductionAchieving optimal anticoagulation during coronary artery bypass graft (CABG) surgery remains a challenge, with variations in heparin response attributed to differences in demographic and clinical factors. Deviations from the target activated clotting time (ACT) during CABG have been linked to adverse outcomes. This study aimed to assess the impact of different intravenous heparin doses on ACT in patients undergoing on-pump CABG. MethodsA cross-sectional study was conducted on 54 patients scheduled for CABG surgery with cardiopulmonary bypass in 2021. ACT measurements were taken 5 min after the initial bolus dose of 200 IU/kg and a secondary dose of 100 IU/kg heparin. Demographic and clinical data, including ACT measures, hemoglobin levels, bypass time, and mortality, were collected. ResultsThe study population predominantly comprised of male patients, with a mean age of 61.18 ± 8.81 years. The patients received 4 (3–4) grafts over 75 (65–80) minutes. Baseline ACT was 149.91±17.48 s, increasing to 410 (359–472) and 604 (542–679) seconds after the initial and additional heparin, respectively. Only 22.2 % of the study subjects achieved target ACT>480 s with 200 IU/kg, and the remaining 77.8 % required an additional 100 IU/kg heparin to reach the target ACT. No cases of heparin resistance, mortality, or dropouts were reported at the end of the study. Preoperative and postoperative hemoglobin levels were positively correlated (r = 0.59, p < 0.0001). ConclusionA 300 IU/kg heparin dose appears safer than lower doses for initiating cardiopulmonary bypass in on-pump CABG. Preoperative hemoglobin optimization may help minimize perioperative hemoglobin drop. Further research is needed to refine dosing strategies and personalize CABG management.

Effect of esketamine on the ED50 of propofol for successful insertion of ureteroscope in elderly male patients: a randomized controlled trial

BackgroundPropofol is effective and used as a kind of routine anesthetics in procedure sedative anesthesia (PSA) for ureteroscopy. However, respiratory depression and unconscious physical activity always occur during propofol-based PSA, especially in elderly patients. Esketamine has sedative and analgesic effects but without risk of cardiorespiratory depression. The purpose of this study is to investigate whether esketamine can reduce the propofol median effective dose (ED50) for successful ureteroscope insertion in elderly male patients.Materials and methods49 elderly male patients undergoing elective rigid ureteroscopy were randomly divided into two groups: SK Group (0.25 mg/kg esketamine+propofol) and SF Group (0.1 µg/kg sufentanil+propofol). Patients in both two groups received propofol with initial bolus dose of 1.5 mg/kg after sufentanil or esketamine was administered intravenously. The effective dose of propofol was assessed by a modified Dixon’s up-and-down method and then was adjusted with 0.1 mg/kg according to the previous patient response. Patients’ response to ureteroscope insertion was classified as “movement” or “no movement”. The primary outcome was the ED50 of propofol for successful ureteroscope insertion with esketamine or sufentanil. The secondary outcomes were the induction time, adverse events such as hemodynamic changes, hypoxemia and body movement were also measured.Result49 patients were enrolled and completed this study. The ED50 of propofol for successful ureteroscope insertion in SK Group was 1.356 ± 0.11 mg/kg, which was decreased compared with that in SF Group, 1.442 ± 0.08 mg/kg (P = 0.003). The induction time in SK Group was significantly shorter than in SF Group (P = 0.001). In SK Group, more stable hemodynamic variables were observed than in SF Group. The incidence of AEs between the two groups was not significantly different.ConclusionThe ED50 of propofol with esketamine administration for ureteroscope insertion in elderly male patients is 1.356 ± 0.11 mg/kg, significantly decreased in comparsion with sufentanil.Trial registrationChinese Clinical Trial Registry, No: ChiCTR2300077170. Registered on 1 November 2023. Prospective registration. http://www.chictr.org.cn.

Prehospital Treatment of Atrial Fibrillation: Infusion Pump for Bolus and Infusion?

Objective The prehospital treatment for stable patients with atrial fibrillation with rapid ventricular response is rate-controlling agents such as calcium channel blockers, often diltiazem given as a bolus. At our agency we encourage the use of a bolus given via the infusion pump over two to four minutes immediately followed by a maintenance infusion, given concerns of recurrent tachycardia or hypotension secondary to rapid bolus administration. We examined if administering a bolus and infusion via an infusion pump shows better heart rate (HR) control at arrival to the emergency department (ED) compared with administration of a bolus only, while maintaining hemodynamic stability during transport. We also analyzed if a patient received a second bolus within 60 min of arrival to the ED. Methods We used a retrospective propensity-matched cohort of prehospital patients with atrial fibrillation for whom diltiazem was administered, from 1/1/2018 to 12/31/2021, in our system of 10 New Jersey paramedic units. We analyzed the age, gender, and initial HR and used it to match groups. We analyzed the mode and time of administration, dosage of the bolus, and presence of hypotension prehospitally. Results The matched groups contained 145 patients who received a prehospital diltiazem bolus only (BO) and 146 patients who received a diltiazem bolus and infusion (BI). There was no significant difference between the mean change in HR from initial paramedic arrival to ED arrival between the two groups (BO 38 vs. BI 34, p = 0.16). There was no significant difference in the need for a second bolus within the first 60 min of arrival to the ED (BO 9.7% vs. BI 11.6%, p = 0.30). Patients in the BO group were more likely to experience prehospital hypotension then in the BI group (BO 17.2% vs BI 8.2%, p = 0.01), despite receiving smaller initial bolus doses (BO 14.2 mg vs. BI 17.4 mg, p < 0.001). Conclusion Our results show no significant differences in HR control or need for repeat bolus at the ED with the use of a diltiazem infusion following a diltiazem bolus. However, even when administering larger boluses, the use of an infusion pump resulted in less hypotension.

Pharmacokinetics of a continuous intravenous infusion of hydromorphone in healthy dogs.

Dosing recommendations for hydromorphone intravenous constant rate infusion (IV CRI) are derived from simulations following IV bolus administration. While this extrapolated dose regimen has been described clinically, pharmacokinetics (PK) of hydromorphone infusions in dogs are not yet described. The study objective was to describe the PK of hydromorphone in healthy dogs receiving an IV bolus followed by an IV CRI for 48 h. A prospective, experimental study was performed involving the administration of hydromorphone (0.1 mg/kg IV bolus then IV CRI 0.01 mg/kg/h over a 48 h period) to 6 healthy Beagle dogs. Blood samples were collected at 16 time points between 0 and 58 h relative to the initial bolus. Plasma hydromorphone concentrations were analyzed by high pressure liquid chromatography with tandem mass spectrometry detection. Pharmacokinetic parameter estimates were obtained with compartmental methods using commercially available software. A two-compartment model with first order elimination was used. At the end of the infusion, median (range) plasma hydromorphone concentrations were 6.8 (5.5-19.6) ng/mL. The median total body clearance was 30.4 (19.8-36.7) mL/min/kg; volume of distribution at steady state was 4.5 (3.2-7.8) L/kg; and terminal elimination half-life was 11.2 (7.6-24.3) h. Hydromorphone (0.1 mg/kg IV bolus then IV CRI of 0.01 mg/kg/h) maintained steady-state plasma concentrations above the minimum human analgesic target in healthy Beagle dogs with minimal side effects. Further studies are needed to determine the effective plasma concentrations of hydromorphone in painful dogs.

Perioperative analgesic management in patients with bladder exstrophy: A clinical study

Background: Bladder exstrophy is a complex, rare congenital malformation with an incidence of 3.3 cases in every 100000 live births and is slightly more common in males. Primary surgical repair requires many hours of surgery with fluid and blood loss. Because of wide fluctuations in hemodynamics, a longer duration of surgery, smaller age, risk of hypothermia and post-operative intensive care may be required. We evaluated the use of continuous caudal epidural infusion of bupivacaine and fentanyl under general anesthesia for urinary bladder exstrophy-epispadias surgery in children. Aims and Objectives: Aim of the study was to evaluate the postoperative analgesia in patients undergoing surgery for bladder exstrophy. The primary objective was to assess the postoperative pain using FLACC scale and sedation score after successful caudal administration. Secondary objective was to assess the hemodynamic changes after caudal administration. Materials and Methods: A total of 13 patients aged between 9months and 13 years of either sex, weighing between 5kg to 30kg, belonging to ASA grade II to IV, underwent surgery for epispadias–exstrophy complex. Initial bolus 0.75ml/kg of 0.25% bupivacaine with fentanyl 1ug/kg was given through epidural. Postoperative analgesia was maintained by continuous infusion of 0.0625% bupivacaine @0.1ml/kg/hr in young children and 0.125% bupivacaine with fentanyl 1ug/ml in older children for 4-5 days with the help of ON-Q pump or infusion pump. Baseline hemodynamic parameters including MAP, heart rate and SpO2 was recorded at various time intervals. Postoperative pain was assessed using face, legs, activity, cry and consolability (FLACC) pain scale and sedation score was assessed by using ramsay sedation score. Results: There was a statistically significant decrease in mean pulse rate in the study group from baseline to thirty minutes after reversal (p&lt;0.001). Similar observation was made for mean arterial pressure which also showed statistically significant decrease from baseline to thirty minutes after reversal (p&lt;0.001). No change was observed in SpO2 from baseline to any other follow-up interval. Conclusion: Perioperative anesthetic and analgesic management of the bladder exstrophy patient can improve the success rate. Epidural bupivacaine with or without fentanyl infusions for short duration can provide safe analgesia.

The use of ferumoxytol for high-resolution vascular imaging and troubleshooting for abdominal allografts.

Ferumoxytol is an ultrasmall superparamagnetic iron oxide which has been used as an off-label intravenous contrast agent for MRI. Unlike gadolinium-based contrast agents, ferumoxytol remains in the intravascular space with a long half-life of 14-21h. During the first several hours, it acts as a blood-pool agent and has minimal parenchymal enhancement. Studies have shown adequate intravascular signal for up to 72h after initial contrast bolus. Ferumoxytol has been shown to be safe, even in patients with renal failure. Ferumoxytol has shown promise in a variety of clinical settings. The exquisite resolution enabled by the long intravascular times and lack of background parenchymal enhancement is of particular interest in the vascular imaging of solid organ allografts. Ferumoxytol magnetic resonance angiography (MRA) may identify clinically actionable findings months before ultrasound, CT angiography, or Gadolinium-enhanced MRA. Ferumoxytol MRA is of particular benefit as a troubleshooting tool in the setting of equivocal ultrasound and CT imaging. In the following review, we highlight the use of ferumoxytol for high-resolution MR vascular imaging for abdominal solid organ allografts, with representative cases.

Stereoselective Pharmacokinetics of Ketamine Administered at a Low Dose in Awake Dogs.

The present study aimed to examine the stereoselective pharmacokinetics of racemic ketamine in dogs at low doses. The secondary aims were to identify associated behavioural effects and propose a ketamine infusion rate. The study was conducted on nine intact male beagles, with each dog undergoing two treatments (BOL and INF). For treatment BOL, an intravenous bolus of 1 mg/kg was administered over 2 min. The treatment INF involved an initial bolus of 0.5 mg/kg given over 1 min, followed by an infusion at 0.01 mg/kg/min for 1 h. Blood samples were collected for pharmacokinetic analysis. The median R/S enantiomer ratio of ketamine remained close to 1 throughout the study. Levels of S-norketamine were significantly higher than those of R-norketamine across all time points. Based on the collected data, the infusion rate predicted to achieve a steady-state racemic ketamine plasma concentration of 150 ng/mL was 0.028 mg/kg/min. Higher scores for behavioural effects were observed within the first five minutes following bolus administration. The most common behaviours observed were disorientation, head movements and staring eyes. Furthermore, employing ROC curve analysis, a racemic ketamine plasma concentration of 102 ng/mL was defined as the cut-off value, correlating with the occurrence of undesirable behavioural patterns.

Heparin Dosing During Percutaneous Coronary Intervention and Obesity.

Unfractionated heparin is the most common anticoagulant used during percutaneous coronary intervention. Practice guidelines recommend an initial weight-based heparin bolus dose between 70 and 100 U/kg to achieve target activated clotting time (ACT) of 250-300 seconds. The impact of severe obesity on weight-based heparin dosing is not well studied. We performed a retrospective analysis of 424 patients undergoing percutaneous coronary intervention who received heparin for anticoagulation. We collected detailed data on cumulative heparin administration and measured ACT values in this cohort. We performed separate analyses to identify clinical predictors that may affect dose-response curves. There was significant variability in dosing with mean dose of 103.9 ± 32-U/kg heparin administered to achieve target ACT ≥ 250 seconds. Women received higher initial heparin doses when adjusted for weight than men (97.6 ± 31 vs. 89 ± 28 U/kg, P = 0.004), and only 49% of patients achieved ACT ≥ 250 s with the initial recommended heparin bolus dose (70-100 U/kg). Lower heparin dose (U/kg) was required in obese patients to achieve target ACT. In multivariate linear regression analysis with ACT as dependent variable, after inclusion of weight-based dosing for heparin, body mass index was the only significant covariate. In conclusion, there is significant variability in the therapeutic effect of heparin, with a lower weight-adjusted heparin dose required in obese patients.

Diagnosis and management of secondary adrenal crisis.

Adrenal crisis (AC) is a life threatening acute adrenal insufficiency (AI) episode which can occur in patients with primary AI but also secondary AI (SAI), tertiary AI (TAI) and iatrogenic AI (IAI). In SAI, TAI and IAI, AC may develop when the HPA axis is unable to mount an adequate glucocorticoid response to severe stress due to pituitary or hypothalamic disruption. It manifests as an acute deterioration in multi-organ homeostasis that, if untreated, leads to shock and death. Despite the availability of effective preventive strategies, its prevalence is increasing in patients with SAI, TAI and IAI due to more frequent exogenous steroid administration, pituitary immune-related effects of immune checkpoint inhibitors and opioid use in pain management. The delayed diagnosis of acute AI which remains infrequently suspected increases the risk of AC. Its main precipitating factors are infections, emotional distress, surgery, cessation or reduction in GC doses, pituitary infarction or surgical cure of endogenous Cushing's syndrome. In patients not known previously to have SAI/TAI/IAI, recognition of its symptoms, signs, and biochemical abnormalities can be challenging and cause delay in proper diagnosis and therapy. Effective therapy of AC is rapid intravenous administration of hydrocortisone (initial bolus of 100mg followed by 200mg/24h as continuous infusion or bolus of 50mg every 6h) and 0.9% saline. In diagnosed patients, preventive education in sick-day rules adjustment of glucocorticoid replacement and hydrocortisone parenteral self-administration must be performed repeatedly by trained health care providers. Strategies to improve the adequate preventive education in patients at risk for secondary AI should be promoted in collaboration with various medical specialist societies and patients support associations.

Comparative evaluation of continuous infusion versus programmed intermittent bolus techniques in erector spinae plane block in modified radical mastectomy - A preliminary randomised controlled trial.

Single-shot erector spinae plane block (ESPB) provides excellent analgesia in mastectomy in the immediate post-operative period but is not sufficient to maintain for prolonged duration. This study compares the efficacy of programmed intermittent bolus (PIB) versus continuous infusion (CI) techniques after ESPB by placing a catheter for mastectomy. After ethical approval and patient consent, ESPB was performed at the T4 level in 50 patients with an initial bolus of 20 mL 0.375% ropivacaine and a catheter placed 30 min before surgery. In the postoperative period, they were randomised to Group I - intermittent bolus of 20 mL 0.2% ropivacaine every 4 h for 24 h and Group C - continuous infusion of 0.2% ropivacaine at 5 mL/h for 24 h. The primary outcome was the 24-h fentanyl consumption by patient-controlled analgesia device. Data was analysed using Stata 14.0. Group I patients had reduced post-operative fentanyl consumption {mean [standard deviation (SD)]: 166 (139.17) µg vs 332 (247.96) µg, P = 0.002} and lower median NRS scores (1 h: 3 vs 5), (2 h: 3 vs 5), (4 h: 3 vs 5), (6 h: 4 vs 5) with a higher mean (SD) Quality of Recovery-15 score {134.4 (8.53) vs 127 (12.89), P = 0.020} compared to Group C, respectively. The 24-h dermatomal sensory coverage was more comprehensive in Group I compared to Group C. The PIB technique after ESPB provides decreased postoperative opioid consumption, better post-operative analgesia and quality of recovery compared to the CI technique in patients undergoing mastectomy.

Anestesia total intravenosa com propofol, cetamina e lidocaína associados à dexmedetomidina ou xilazina para cirurgia de ovário-histerectomia em cadelas

ABSTRACT: This study compared cardiovascular and respiratory effects of dexmedetomidine and xylazine in total intravenous anesthesia with propofol, ketamine, and lidocaine. Twenty-one female dogs were submitted to ovariohysterectomy, premedicated with acepromazine and anesthetized with propofol at a variable rate. The dogs were intubated and supplemented with 100% oxygen in a circuit without rebreathing gases in spontaneous ventilation. They were divided into three groups (n=21) after induction: control (CON) with ketamine (2 mg/kg + 0.6 mg/kg/h) and lidocaine (2 mg/kg + 3 mg/kg/h), DEX and XIL with the same drugs as CON, associated with dexmedetomidine (2 µg/kg + 1 µg/kg/h) or xylazine (0.2 mg/kg + 0.1 mg/kg/h). Propofol consumption, fentanyl analgesic rescue, and cardiorespiratory and blood gas parameters were evaluated during anesthesia. The DEX group had a lower consumption of propofol (0.16 ± 0.09 mg/kg/min) compared to CON (0.24 ± 0.09 mg/kg/min), both not differing from XIL (0.23 ± 0.09 mg/kg/min). The mean arterial pressure was higher after the initial bolus in DEX (107 ± 8 mmHg) and XIL (96 ± 11 mmHg) compared to the CON group (80 ± 10 mmHg). Higher accumulation of arterial carbon dioxide and a decrease in pH were observed in the CON group. The total number of fentanyl rescues did not differ between DEX (7) and XIL (6) and were lower than CON (16). Therefore, dexmedetomidine and xylazine reduced intraoperative fentanyl consumption compared to ketamine and lidocaine infusion alone. However, only dexmedetomidine promoted lower propofol consumption and higher blood pressure values.

Efficacy and safety of fospropofol disodium sedation for same-day bidirectional endoscopy in elderly patients: protocol for a prospective, single-center, randomized, double-blind, non-inferiority trial.

Fospropofol disodium is a novel prodrug that has improved pharmacokinetic and pharmacodynamic properties when compared with propofol. This trial aims to compare the efficacy and safety of fospropofol versus propofol sedation for same-day bidirectional endoscopy in elderly patients. This is a prospective, single-center, double-blind, randomized, propofol-controlled, non-inferiority trial. A total of 256 patients aged 65years or older, who are scheduled for same-day bidirectional endoscopy under sedation, will be randomly allocated, in a 1:1 ratio, to either fospropofol group or propofol group (n = 128 in each group). All patients will receive analgesic pre-treatment with sufentanil 5μg. Two minutes later, an initial bolus dose of fospropofol 6.5mg/kg or 1.5mg/kg propofol and supplemental doses of fospropofol 1.6mg/kg or 0.5mg/kg propofol will be titrated as needed to achieve target sedation levels during the procedures. The primary outcome is the success rate of same-day bidirectional endoscopy. Secondary outcomes include the time to successful induction of sedation, duration, time to being fully alert, time to patient discharge, endoscopist satisfaction, patient satisfaction, and the top-up frequency and dosage of sedative medications. The safety endpoints consist of adverse events concerning cough reflex, gag reflexes, body movement, muscular tremor, and pain on injection. Sedation-related AEs, including episodes of desaturation, severe desaturation (SpO2 < 90%), hypotension, severe hypotension (decrease in MBP ≥30% of baseline), and bradycardia, will also be recorded. Data will be analyzed on an intention-to-treat basis. We hypothesize that the efficacy and safety of fospropofol sedation for elderly patients undergoing same-visit bidirectional endoscopy will not be inferior to that of propofol. Our findings will potentially provide a new sedation regimen for same-visit bidirectional endoscopy in elderly patients. clinicaltrials.gov, identifier NCT02875639.