Hemodynamic Side Effects Research Articles

Intravenous morphine versus intravenous paracetamol after cardiac surgery in neonates and infants: a study protocol for a randomized controlled trial

BackgroundMorphine is worldwide the analgesic of first choice after cardiac surgery in children. Morphine has unwanted hemodynamic and respiratory side effects. Therefore, post–cardiac surgery patients may potentially benefit from a non-opioid drug for pain relief. A previous study has shown that intravenous (IV) paracetamol is effective and opioid-sparing in children after major non-cardiac surgery. The aim of the study is to test the hypothesis that intermittent IV paracetamol administration in children after cardiac surgery will result in a reduction of at least 30% of the cumulative morphine requirement.MethodsThis is a prospective, multi-center, randomized controlled trial at four level-3 pediatric intensive care units (ICUs) in the Netherlands and Belgium. Children who are 0–36 months old will be randomly assigned to receive either intermittent IV paracetamol or continuous IV morphine up to 48 h post-operatively. Morphine will be available as rescue medication for both groups. Validated pain and sedation assessment tools will be used to monitor patients. The sample size (n = 208, 104 per arm) was calculated in order to detect a 30% reduction in morphine dose; two-sided significance level was 5% and power was 95%.DiscussionThis study will focus on the reduction, or replacement, of morphine by IV paracetamol in children (0–36 months old) after cardiac surgery. The results of this study will form the basis of a new pain management algorithm and will be implemented at the participating ICUs, resulting in an evidence-based guideline on post-operative pain after cardiac surgery in infants who are 0–36 months old.Trial registrationDutch Trial Registry (www.trialregister.nl): NTR5448 on September 1, 2015. Institutional review board approval (MEC2015–646), current protocol version: July 3, 2017

Translational Advances of Hydrofection by Hydrodynamic Injection.

Hydrodynamic gene delivery has proven to be a safe and efficient procedure for gene transfer, able to mediate, in murine model, therapeutic levels of proteins encoded by the transfected gene. In different disease models and targeting distinct organs, it has been demonstrated to revert the pathologic symptoms and signs. The therapeutic potential of hydrofection led different groups to work on the clinical translation of the procedure. In order to prevent the hemodynamic side effects derived from the rapid injection of a large volume, the conditions had to be moderated to make them compatible with its use in mid-size animal models such as rat, hamster and rabbit and large animals as dog, pig and primates. Despite the different approaches performed to adapt the conditions of gene delivery, the results obtained in any of these mid-size and large animals have been poorer than those obtained in murine model. Among these different strategies to reduce the volume employed, the most effective one has been to exclude the vasculature of the target organ and inject the solution directly. This procedure has permitted, by catheterization and surgical procedures in large animals, achieving protein expression levels in tissue close to those achieved in gold standard models. These promising results and the possibility of employing these strategies to transfer gene constructs able to edit genes, such as CRISPR, have renewed the clinical interest of this procedure of gene transfer. In order to translate the hydrodynamic gene delivery to human use, it is demanding the standardization of the procedure conditions and the molecular parameters of evaluation in order to be able to compare the results and establish a homogeneous manner of expressing the data obtained, as ‘classic’ drugs.

Balanced anesthesia with remifentanil and desflurane: Clinical considerations for dose adjustment in adults

The intraoperative combination of volatile anesthetics with opioids is a well-accepted technique because of its hemodynamic stability and side effects. This study in adults was designed to determine the pharmacodynamic interactions between different dosages of remifentanil and desflurane in response to skin incision. A total of 60 patients were enrolled in this study. Patients were prospectively randomized to receive 0, 0.1, 0.15, or 0.25 microg/kg/min remifentanil. Anesthesia was induced with remifentanil, propofol, and succinylcholine. Thereafter, a group-specific desflurane concentration was administered using Dixon's up-and-down technique. After a "wash out" and equilibration period, patients were observed for defense movements up to 1 minute after skin incision. Mean arterial pressure and heart rate were recorded before induction of anesthesia (baseline), at surgical incision, as well as 2 and 4 minutes thereafter. Time until extubation was assessed after stopping desflurane and remifentanil at the end of the surgery. Remifentanil at 0.1, 0.15, or 0.25 microg/kg/min reduced desflurane requirements by 74, 83, and 90 percent, respectively. The time course of mean arterial pressure did not differ between the study groups. However, compared with the group without remifentanil, heart rate was significantly lower in patients receiving 0.15 or 0.25 microg/kg/min remifentanil. No difference between the groups was observed with regard to extubation time. Remifentanil reduces in a dose-dependent manner the desflurane requirements for skin incision without increasing recovery time. An infusion rate higher than 0.1 microg/kg/min results in a significantly decreased heart rate.

Inactivated antithombin as anticoagulant reversal in a rat model of cardiopulmonary bypass: a potent and potentially safer alternative to protamine.

Heparin anticoagulation followed by protamine reversal is commonly used in cardiopulmonary bypass (CPB). As an alternative to protamine, a recombinant inactive antithrombin (riAT) was designed as an antidote to heparin and was previously shown to be as potent as protamine in-vitro. In the present study, riAT was assessed for its ability to neutralize heparin after CPB in a rat model. After 60min of CPB under heparin, rats received 5mg/kg protamine, 37.5mg/kg riAT or phosphate buffered saline (PBS) as placebo. Residual anticoagulant activity was assessed using the activated partial thromboplastin time assay before, and 10-30min after reversion. Haemodynamic monitoring was performed and plasma histamine concentration was also measured. In this model, riAT appeared to be as efficient as protamine in neutralizing heparin. Ten minutes after injection, riAT and protamine both decreased heparin activity, to 1.8±1.3 and 4.5±1.4u/ml, respectively (23.1±5.1u/ml in placebo group). Furthermore, evolution of mean carotid arterial pressure, heart rate and plasma histamine levels was comparable in rats treated with PBS or riAT, while protamine exhibited haemodynamic side effects and increased histamine plasma concentration. Thus, riAT could represent an advantage over protamine in CPB because it efficiently reverses heparin activity without negative effects on haemodynamic parameters and plasma histamine level.

Comparison of a loading dose of dexmedetomidine combined with propofol or sevoflurane for hemodynamic changes during anesthesia maintenance: a prospective, randomized, double-blind, controlled clinical trial

BackgroundThere may be great individual variability in the hemodynamic effects of this dexmedetomidine. For this reason, the dose must be carefully adjusted to achieve the desired clinical effect. Whether a loading dose of dexmedetomidine produces hemodynamic side effects during the anesthesia maintenance is unknown. The aim of this study was to compare the effects of a loading dose of dexmedetomidine combined with propofol or sevoflurane on hemodynamics during anesthesia maintenance.MethodsEighty-four patients who were scheduled for general surgery under balanced general anesthesia were randomly allocated into 4 groups (n = 21): the propofol and dexmedetomidine group, the sevoflurane and dexmedetomidine group, the propofol and normal saline group, or the sevoflurane and normal saline group. The hemodynamic indexes at the time of just before, 5 min after and the end of study drug infusion (dexmedetomidine or normal saline) were recorded. The incidence rates of increasing blood pressure at the end of study drug infusion (greater than 20% compared to baseline or before study drug infusion) were evaluated.ResultsMean arterial pressure increased significantly (P < 0.01) only in the propofol and dexmedetomidine group after intravenous dexmedetomidine compared administration. 80% of cases with propofol and dexmedetomidine had increased mean arterial blood pressure compared to only 5% of cases in the sevoflurane and dexmedetomidine group (P < 0.05). Heart rates in the propofol and dexmedetomidine and the sevoflurane and dexmedetomidine groups decreased significantly after dexmedetomidine infusion (P < 0.01).ConclusionsIntraoperative administration of a loading dose of dexmedetomidine combined with propofol in anesthesia maintenance proceeded a significant increase in blood pressure. In contrast, it combines with sevoflurane didn’t produce increased blood pressure. Meanwhile it is not unexpected that dexmedetomidine combined with propofol or sevofurance decreased heart rate, due to the known side effects of DEX. Therefore, dexmedetomidine should be used cautiously during the entire intravenous anesthesia maintenance period, especially during maintenance with propofol.Trial registrationChinese Clinical Trial Registry, ChiCTR-IOR-17010423, registered on 13 January 2017.

Abstract TP95: Intra-arterial Interleukin-1 alpha is Well Tolerated and Neuroprotective After Experimental Ischemic Stroke

Endovascular thrombectomy combined with t-PA is the current standard of care for emergent large vessel occlusion (ELVO) stroke. Unfortunately, despite rising recanalization rates, stroke remains the leading cause of long-term disability worldwide suggesting that additional therapies are needed. Severe stroke morbidity may be due, partially, to the acute and sustained inflammatory stroke response. Preclinical research has shown some promise with anti-inflammatory agents in limiting brain injury and improving functional outcome; however, the post-stroke inflammatory cascade appears to have both beneficial and deleterious effects making the translation of such anti-inflammatory approaches perilous. We aim to show that the inflammatory cytokine interleukin-1alpha (IL-1α) is well-tolerated, neuroprotective, and conveys functional benefit after ischemic stroke. 3-month-old C57/BL6 mice were subjected to MCAo and given IL-1α via IV injection or IA infusion upon recanalization. Mice were allowed to recover for 7 days before sacrifice. Brains were flash frozen for IHC and serum for high sensitivity ELISA. We noted that IV IL-1α (1 ng) is neuroprotective (as measured by cresyl violet stained infarct volumes) and significantly improved functional recovery in open field behavioral tests. When given IV, IL-1α showed transient hemodynamic side effects that are typical of IL-1α’s known physiologic functions (fever, sterile inflammation, etc.) These effects are short lived with systemic (IV) administration and IA IL-1α (0.1 ng) administration showed neuroprotection without the side effects seen with IV treatment. Additionally, we noted that IL-1α is directly neuroprotective of primary mouse cortical neurons exposed to oxygen and glucose deprivation conditions in vitro . IL-1α’s profound, direct neuroprotective effects and its functional benefit, make IL-1α an attractive target for future study in ischemic stroke.

Drugs for intravenous induction of anesthesia: propofol

In aseries of articles dealing with hypnotics for induction of anesthesia, this article describes the development and current value of propofol. Its significance far exceeds that of apure induction hypnotic (sedation in diagnostic and therapeutic procedures and on the intensive care unit). Propofol is also used for sedation in diagnostic and therapeutic procedures and on the intensive care unit. In the field of induction of anesthesia, the alternatives are barely used. Some contraindications are still controversial whereas others are no longer sufficiently anchored in the users' awareness (widespread off-label use). Adverse effects, such as injection pain, infection risk and propofol-related infusion syndrome (PRIS) could be significantly reduced by pharmacovigilance. With appropriate caution nearly the whole spectrum of anesthesiology patients can be treated using propofol. The hemodynamic side effects and the rare but potentially fatal PRIS are limitations. Further developments address the water solubility and the solubilizing agents of propofol.

Comparison of Anesthetic Properties of Ketofol (Ketamine with Propofol) and Propofol in Minor Surgical Procedures

Introduction: Outpatient anesthesia for the minor day care surgical procedures requires a safe anesthesia and anesthetic agents. For this purpose two study solutions propofol with ketamine (ketofol) and propofol were compared. The comparison of the both agents were assessed, evaluated and discussed in this study. Methodology: This is prospective study of 100 adult patients of both sex aged between 18-60 years with ASA physical status class I and II who were operated in the Birat Medical College teaching hospital. This study was started after approval from the ethical committee of the hospital and after written and informed consent from all participants. All patients were randomly divided into two groups. Group A (n=50) received ketamine with propofol and Group B (n=50) propofol after intravenous sedation with 2 mg of midazolam and 1 mg of butorphanol. The main aim of this study was comparison of onset of sedation, respiratory and cardiac adverse events, level of sedation using Ramsey sedation scale, requirement of sedatives, recovery time, average cost of the sedatives and postoperative complications between the two groups. All collected data are analyzed using MS Excel office 2007 and for the data analysis IBM SPSS software was used.Results: In the both groups patients were comfortable with the either anesthetic agents. Onset of anesthesia was faster in Group A. Intraoperative sedation was measured using Ramsay sedation scale and was comparable. Recovery from sedation was assessed with AVPU scale and patient was shifted to postoperative room after the verbal response. Postoperative complications seen were nausea vomiting, severe pain, ketamine induced psychotomimetic effects and all of these were treated well and discharged on the same day from the hospital.Conclusion: The combination of ketamine and propofol for the sedation in minor surgical procedures has more advantages than the propofol alone. The combination is cost effective, has better sedation and hemodynamic stability, quick recovery and fewer side effects in the post operative room. Birat Journal of Health SciencesVol.2/No.3/Issue 4/Sep- Dec 2017, Page: 287- 291

The Sedative and Propofol-Sparing Effect of Dexmedetomidine and Midazolam as Premedicants in Minor Gynecological Day Care Surgeries: A Randomized Placebo-Controlled Study.

Background and Aims:Ambulatory surgery is continually evolving specialty in the majority of surgical procedures. Dexmedetomidine and midazolam are newer adjuvants for sedation and reducing the dose of anesthetic agents. The aim of this study was to compare the sedative and propofol-sparing effect of dexmedetomidine and midazolam in minor gynecological day care surgeries. Observer's Assessment of Activity and Sedation, dose of additional propofol, Aldrete and street fitness score were studied as primary outcomes. Hemodynamic parameters and side effects were evaluated as secondary outcomes.Materials and Methods:A prospective randomized placebo-controlled study was conducted on 150 American Society of Anesthesiologists ASA physical status Classes I and II gynecological patients between 18 and 50 years and were allocated into three groups of fifty each. Group A received intravenous (i.v.) dexmedetomidine 0.1 μg/kg, Group B received i.v. midazolam 0.04 mg/kg, and Group C received normal saline 10 min before induction.Results:Sedation score was statistically highly significant between Group A and B (P < 0.001). Between Group A and C, it was statistically significant (P < 0.05); however, score was nonsignificant between Groups B and C (P > 0.05). During recovery at 120 min after surgery, score 5 was achieved equally by all three groups which was found to be statistically insignificant (P > 0.05). Mean dose of additional propofol used was less in Group A (14 ± 9.25) than B (25 ± 5.40) and C (53 ± 10.96). On intergroup comparison between all three groups, it was found to be statistically highly significant (P < 0.001). Comparison of bispectral index (BIS) values between Groups A and C and Groups B and C were highly significant (P < 0.001). However, it was statistically significant between Groups A and B (P < 0.05). Aldrete scoring and street fitness scores were highly significant between Groups A and B, B and C, and also between Groups A and C (P < 0.001). No significant hemodynamic derangements and side effects were noted in any of three groups.Conclusion:Dexmedetomidine had good sedation and better recovery characteristics than midazolam. BIS monitoring was helpful in maintaining the depth of anesthesia.

Ropivacaine has no advantage over bupivacaine in thoracic epidural analgesia for patients with pectus excavatum undergoing the Nuss procedure - a single blind randomized clinical trial comparing efficacy and safety.

IntroductionPectus excavatum repair (Nuss procedure) is a painful procedure requiring effective postoperative analgesia.AimTo establish whether thoracic epidural analgesia with ropivacaine is non-inferior to epidural analgesia with bupivacaine following the Nuss procedure in children.Material and methodsThe prospective, randomized, controlled, single blind study included 81 children. Computer-generated random numbers were used to allocate treatment. All children received general anesthesia. Intraoperative and postoperative analgesia was achieved with either 0.5% and 0.1% ropivacaine (group R) or 0.375% and 0.0625% bupivacaine (group B). The Numeric Rating Scale (NRS) and the Prince Henry Hospital Pain Score (PHHPS) were used to assess postoperative pain directly after and 1, 8, 20 and 24 hours after awakening from general anesthesia. NRS scores of more than 2 and a PHHPS score of more than 1 were considered as pain requiring intervention. Hemodynamic stability and side effects were also compared between the groups.ResultsThe durations of the procedure and extubation times in groups R and B were similar (59 ±7 vs. 56 ±10 minutes and 9 ±5 vs. 10 ±5 minutes, respectively). Pain scores requiring intervention were below 10% and were recorded with similar frequency in both groups, except for one difference in the PHHPS score in favor of group R after 24 hours (12% vs. 40%, p < 0.05). The frequency of side effects and hemodynamic stability were similar in both groups.Conclusions0.1% epidural ropivacaine has no advantage over 0.0625% epidural bupivacaine for pectus excavatum repair in children.

Comparison of Intrathecal Nalbuphine Hydrochloride and Clonidine Hydrochloride as an Adjuvant to Hyperbaric Bupivacaine in Abdominal Hysterectomy.

Background:Various adjuvants for prolongation of intraoperative and postoperative analgesia have been clinically studied in the literature.Aim:This study was done to evaluate and compare the effects of nalbuphine and clonidine as an adjuvant to bupivacaine in spinal anesthesia.Methods:In this prospective, randomized, placebo control, double-blind, and comparative study, a total of ninety patients of American Society of Anesthesiologists physical status Classes I and II undergoing abdominal hysterectomy under subarachnoid block were randomly divided into three groups. In addition to 15 mg of 0.5% hyperbaric bupivacaine administered, patients of groups BS, BN, and BC received 0.9% normal saline, 1.6 mg nalbuphine, and 30 μg clonidine, respectively. The total volume of drugs administered intrathecally was made up to 3.5 ml by addition of sterile isotonic normal saline in all. The onset time and duration of sensory and motor block, duration of analgesia, and total dose of postoperative analgesic requirement in the first 24 h were compared among groups. Hemodynamic changes and side effects were also recorded.Results:Addition of study adjuvants brought significantly faster onset of sensory and motor block. Patients in clonidine group showed significantly longer mean time two segment sensory block regression (P < 0.05) lowest seen in control group. The regression time of motor block to modified Bromage Grade I was significantly longer in clonidine group and comparable in the other groups. Adjuvants have significantly increased the mean duration of analgesia, highest in clonidine group (P < 0.05).Conclusion:Intrathecal clonidine is associated with prolonged motor and sensory block, better hemodynamic stability, and less postoperative analgesic requirement as compared to nalbuphine.

Comparison of ketamine with midazolam versus ketamine with fentanyl for pediatric extracorporeal shock wave lithotripsy procedure: A randomized controlled study

Objectives:To compare the effects of ketamine-fentanyl (KF) and ketamine-midazolam (KM) combinations on hemodynamic parameters, recovery properties, pain, and side effects in pediatric patients undergoing extracorporeal shock wave lithotripsy (ESWL) procedure.Methodology:In this double-blinded, randomized trial, 60 pediatric patients aged between 1 and 13 years with American Society of Anesthesiologists physical status Classes I and II, who scheduled for ESWL procedure, were included in the study. Patients were randomly divided into two groups: Group KM received 0.1 mg/kg of midazolam +1–1.5 mg/kg of ketamine and Group KF received 1 μg/kg of fentanyl +1–1.5 mg/kg of ketamine intravenously.Results:There were similar demographic properties, recovery, and discharge times between groups. No statistically significant difference was found in peripheral oxygen saturation, mean and diastolic blood pressure, Ramsey sedation scores, modified Aldrete recovery scores, side effects, and recovery times (Group KM, 16.067 ± 1.2 min; Group KF, 19.46 ± 0.86 min) between groups (P > 0.05).Conclusion:KF combination offers better hemodynamic properties, less side effects with lower visual analog scores, and face, legs, activity, cry, and consolability scores than KM in the pediatric ESWL procedure.

Propofol–midazolam versus propofol–dexmedetomidine as a deep sedation for endoscopic retrograde cholangio-pancreaticoduodenoscopy

Background Endoscopic retrograde cholangio-pancreaticoduodenoscopy (ERCP) is a day procedure for diagnostic or therapeutic biliary problems. Many kinds of sedation are used to provide patients comfort and facilitate work. Propofol and midazolam is the preferred cocktail. Dexmedetomidine with sedo-analgesic properties makes it another suitable regimen. The aim of this study was to compare the efficacy of adding either midazolam or dexmedetomidine to propofol for procedural sedation during ERCP. Patients and methods This study was conducted in Mansoura University Hospitals, Gastroenterology Center. A total of 84 patients (40–80 years), American Society of Anesthesiologist II, III, and IV scheduled for ERCP were randomly allocated into two groups: the PM group received propofol–midazolam and the group PD received propofol–dexmedetomidine. Heart rate, mean arterial blood pressure, and SpO2 were recorded at basal, intraoperative, postanesthesia care unit (PACU), till discharge. O2 desaturation, total dose of propofol, intraoperative complications, patients, and surgeon satisfaction were recorded. Results Heart rate and mean arterial blood pressure showed a significant reduction in group D compared with group M. Onset of deep sedation shows a significant reduction in group D versus group M. Recovery time and onset of discharge from the postanesthesia care unit shows statistically significant prolongation in group D versus group M. The total dose of propofol, intraoperative complications and also surgeon and patient satisfaction were comparable. Conclusion Administration of 1-μg/kg loading dose of dexmedetomidine or midazolam 1 mg intravenous, followed by intravenous propofol (1 mg/kg) and then 10 mg increments can produce an effective and smooth sedation without causing hemodynamic or respiratory side effects. So, dexmedetomidine could be an important alternative to midazolam for sedation in ERCP and other short procedures.

Hemodynamic variables and side effects of 0.75% preservative free Ropivacaine for lower abdominal surgeries

Hemodynamic variables and side effects of 0.75% preservative free Ropivacaine for lower abdominal surgeries

A Study Comparing Propofol Auto-coinduction and Standard Propofol Induction in Patients Undergoing General Anesthesia Without Midazolam Pretreatment: A Prospective Randomized Control Trial.

Background:Propofol has emerged as an induction agent of choice over the past two decades due to its quick, smooth induction and rapid recovery. The main concern for an anesthesiologist is the hemodynamic instability caused by the standard induction dose of propofol (2–3 mg/kg).Aim:We aim to study the efficacy of propofol auto-coinduction technique in comparison to the standard propofol induction technique in terms of the total induction dose requirement of propofol, the incidence of hemodynamic side effects and pain on injection, and the incidence of fentanyl-induced cough (FIC) in the absence of a synergistic agent like midazolam.Materials and Methods:This was a prospective, observer-blinded, randomized controlled trial. The study was initiated after obtaining the institutional ethics committee approval and is registered in the Clinical Trials Registry India. Eighty American Society of Anesthesiology Physical Status I and II patients, of either sex, aged between 18 and 55 years, and scheduled for elective surgeries under general anesthesia were randomized into two equal groups. Patients allocated to Group I (auto-coinduction) received 20% of the calculated dose of injection propofol 2 mg/kg (i.e., 0.4 mg/kg) as the priming dose followed by injection fentanyl 1 μg/kg after 1 min and the remaining propofol was administered in titrated doses till loss of verbal response after 2 min. In Group II (control), patients received injection fentanyl 1 μg/kg followed by single bolus dose of injection propofol up to 2 mg/kg till loss of verbal response. Midazolam was not used for premedication or induction. Intubation was carried out only after ensuring achievement of optimum depth of anesthesia using bispectral index scale. The total dose of propofol administrated for induction, occurrence of pain on injection, severity of cough after fentanyl administration, hemodynamic parameters, and apneic episodes were recorded.Statistical Analysis:All data were expressed as mean ± 2 standard deviation. For statistical analysis, SPSS software version 16 (SPSS Inc., 2007, Chicago, IL, USA) was used.Results:The mean dose of injection propofol required for induction was significantly lower in Group I (67.0 ± 17.9 mg) when compared with Group II (111.3 ± 17.6 mg) (P < 0.01). The mean heart rate was significantly higher (P < 0.01) and the mean blood pressure was significantly lower in Group II (P < 0.01) when compared to Group I at 1 min postinduction, immediately after intubation, and 5 min after induction. The incidence of complications such as hypotension, pain on injection, and FIC was higher in Group II (50%) as compared to Group I (18%).Conclusion:In our study, we found that the induction dose requirement of propofol was significantly lower in the auto-coinduction group when compared to the conventional induction group. The auto-coinduction technique offered a stable hemodynamic profile, reduced pain on injection, and less incidence of FIC as compared to the conventional propofol induction technique.

Clonidine - An ideal premedicant for attenuation of haemodynamic side effects of intravenous Ketamine anaesthesia

Clonidine - An ideal premedicant for attenuation of haemodynamic side effects of intravenous Ketamine anaesthesia

Analgosedation in paediatric severe traumatic brain injury (TBI): practice, pitfalls and possibilities

Analgosedation is a fundamental part of traumatic brain injury (TBI) treatment guidelines, encompassing both first and second tier supportive strategies. Worldwide analgosedation practices continue to be heterogeneous due to the low level of evidence in treatment guidelines (level III) and the choice of analgosedative drugs is made by the treating clinician. Current practice is thus empirical and may result in unfavourable (often hemodynamic) side effects. This article presents an overview of current analgosedation practices in the paediatric intensive care unit (PICU) and addresses pitfalls both in the short and long term. We discuss innovative (pre-)clinical research that can provide the framework for initiatives to improve our pharmacological understanding of analgesic and sedative drugs used in paediatric severe TBI and ultimately facilitate steps towards evidence-based and precision pharmacotherapy in this vulnerable patient group.

Xenon as an adjuvant to sevoflurane anesthesia in children younger than 4years of age, undergoing interventional or diagnostic cardiac catheterization: A randomized controlled clinical trial.

Xenon has repeatedly been demonstrated to have only minimal hemodynamic side effects when compared to other anesthetics. Moreover, in experimental models, xenon was found to be neuroprotective and devoid of developmental neurotoxicity. These properties could render xenon attractive for the anesthesia in neonates and infants with congenital heart disease. However, experience with xenon anesthesia in children is scarce. We hypothesized that in children undergoing cardiac catheterization, general anesthesia with a combination of sevoflurane with xenon results in superior hemodynamic stability, compared to sevoflurane alone. In this prospective, randomized, single-blinded, controlled clinical trial, children with a median age of 12 [IQR 3-36] months undergoing diagnostic/interventional cardiac catheterization were randomized to either general anesthesia with 50-65vol% xenon plus sevoflurane or sevoflurane alone. The primary outcome was the incidence of intraprocedural hemodynamic instability, defined as the occurrence of: (i) a heart rate change >20% from baseline; or (ii) a change in mean arterial blood pressure >20% from baseline; or (iii) the requirement of vasopressors, inotropes, chronotropes, or fluid boluses. Secondary endpoints included recovery characteristics, feasibility criteria, and safety (incidence of emergence agitation and postoperative vomiting. After inclusion of 40 children, the trial was stopped as an a priori planned blinded interim analysis revealed that the overall rate of hemodynamic instability did not differ between groups [100% in both the xenon-sevoflurane and the sevoflurane group. However, the adjuvant administration of xenon decreased vasopressor requirements, preserved better cerebral oxygen saturation, and resulted in a faster recovery. Xenon anesthesia was feasible (with no differences in the need for rescue anesthetics in both groups). Our observations suggest that combining xenon with sevoflurane in preschool children is safe, feasible, and facilitates hemodynamic management. Larger and adequately powered clinical trials are warranted to investigate the impact of xenon on short- and long-term outcomes in pediatric anesthesia.

Dexmedetomidine pharmacodynamics in healthy volunteers: 2. Haemodynamic profile

BackgroundDexmedetomidine, a selective α2-adrenoreceptor agonist, has unique characteristics, with little respiratory depression and rousability during sedations. We characterized the haemodynamic properties of dexmedetomidine by developing a pharmacokinetic–pharmacodynamic (PKPD) model with a focus on changes in mean arterial blood pressure (MAP) and heart rate. MethodsDexmedetomidine was delivered i.v. to 18 healthy volunteers in a step-up fashion by target-controlled infusion using the Dyck model. Exploratory PKPD modelling and covariate analysis were conducted in NONMEM. ResultsOur model adequately describes dexmedetomidine-induced hypotension, hypertension, and bradycardia, with a greater effective concentration for the hypertensive effect. Changes in MAP were best described by a double-sigmoidal Emax model with hysteresis. Covariate analysis revealed no significant covariates apart from age on the baseline MAP in the population pharmacokinetic model used to develop this PKPD model. Simulations revealed good general agreement with published descriptive studies of haemodynamics after dexmedetomedine infusion. ConclusionsThe present integrated PKPD model should allow tighter control over the desired level of sedation, while limiting potential haemodynamic side-effects. Clinical trial registrationNCT01879865.

The effect of surgical technique on hemodynamics, arterial oxygenation and pulmonary mechanics in radical prostatectomy operations.

The effects of surgical technique on respiratory mechanics, arterial oxygenation and hemodynamics in radical prostatectomy operation were investigated. The study was planned on ASA II-III, 40-65 years old, fourty patients scheduled for radical prostatectomy under general anesthesia. They were divided into two groups: perineal and suprapubic (Group P, n = 20; Group S, n = 20). Heart rate, mean arterial blood pressure, arterial oxygen saturation (SpO2), partial pressure of end-tidal carbon dioxide (PEtCO2), Peak inspiratory pressure (PIP), plato pressure (Pplato), partial pressure of oxygen in arterial blood (PaO2), partial pressure of carbon dioxide in arterial blood (PaCO2) values were evaluated at 10 minutes after induction. After the position applied for surgery in the 30.60 and 90th minutes, the Alveolar-arterial oxygen pressure gradient (P(A-a) O2), the ratio of physiologic dead space over tidal volume (VD/VT), arterial to end tidal CO2 gradient (P(a-et) CO2), static compliance (CS), dynamic compliance (CD) were assessed. In the assessment of groups, there were not statistical differences about mean blood pressure, heart rate, SpO2, PetCO2, PaO2, plateau pressure, and P (A-a) values (p &gt; 0.05). Peak inspiratory pressure was higher in Group P. Peak inspiratory pressure and plateau pressure increased with CO2 insufflation in Group P. PaCO2 and P(a-et) CO2 were higher statistically significantly in Group 0. There was no difference in terms of the PetCO2 values. VD/VT ratios were statistically significantly lower in the Group P. Suprapubic surgery was shown to improve oxygenation and respiratory mechanics without causing any hemodynamic side effect in radical prostatectomy operation.