To compare the pharmacokinetics, pharmacodynamics and the concentration-effect relationship of rocuronium in patients under stable propofol or isoflurane anesthesia.
Ten patients were randomized to ...receive fentanyl, propofol and nitrous oxide (60%) or fentanyl, thiopental, isoflurane (1.2% end-tidal concentration) and nitrous oxide (60%). To obtain good intubation conditions and maintain adequate muscle relaxation during surgery, patients received two bolus doses of rocuronium: 0.5 mg x kg(-1) (1.7 x ED95) at induction followed one hour later by 0.3 mg x kg(-1) (1 x ED95). Arterial blood samples were obtained over six hours after the second bolus dose. Plasma concentrations of rocuronium were measured using high pressure liquid chromatography. Muscle twitch tension was monitored by mechanomyography for the two doses. Pharmacokinetic and pharmacodynamic parameters were determined.
No differences in rocuronium pharmacokinetic parameters were observed between both groups. After the second bolus, clinical duration was 20 +/- 6 min in the propofol group vs 39 +/- 8 min in the isoflurane group (P <0.05). The effect compartment concentration corresponding to 50% block, EC50, was higher under propofol anesthesia: 1008 vs 592 microg x L(-1) (P <0.05).
Rocuronium body disposition is similar under stable propofol or isoflurane anesthesia. In contrast to isoflurane, propofol does not prolong the neuromuscular block. Therefore, the potentiating effect of isoflurane is of pharmacodynamic origin only, as explained by an increased sensitivity at the neuromuscular junction. In contrast with isoflurane anesthesia where the dose of rocuronium has to be decreased under stable conditions, no dose adjustment is required under propofol anesthesia.
Dipeptidyl peptidase-3 (DPP3) is a protease involved in the degradation of several cardiovascular mediators. Adrenomedullin (bio-ADM) is a peptide essential for regulation of endothelial barrier ...function. In different shock-pathologies, both biomarkers are associated with disease severity, organ dysfunction and mortality. Associations with outcome in critically ill COVID-19 patients are unknown. The objectives of the present study were to investigate associations of bio-ADM and "circulating DPP3" (cDPP3) with short-term outcome in critically ill COVID-19 patients (n=80).
A multicentre prospective cohort study was performed. The primary end-point was 28-day mortality. Secondary end-points included different severities of acute kidney injury (AKI).
cDPP3 levels were mainly associated with 28-day mortality; Area under the receiver operating characteristics (AUROCs) of 0.69 (0.56-0.82, p=0.023), 0.77 (0.64-0.90, p<0.001) and 0.81 (0.65-0.96, p<0.001) at admission, day 3 and day 7, respectively. In contrast, bio-ADM levels were mainly associated with AKI, with AUROCs of 0.64 (0.51-0.77, p=0.048), 0.75 (0.64-0.86, p<0.001) and 0.83 (0.74-0.93, p<0.001) for day 1, 3 and 7, respectively. Interestingly, patients with high levels of both cDPP3 and bio-ADM at day 7 had an additionally increased risk of 28-day mortality (hazard ratio 11.8; 95% CI 2.5-55.3, p<0.001).
cDPP3 and bio-ADM responses were associated with short-term mortality and AKI in critically ill COVID-19 patients, respectively. These findings suggest that treatment with specific antibodies modulating cDPP3 or bio-ADM-related pathways may improve outcome of COVID-19.
The present study aimed at assessing the prevalences of post-traumatic stress disorder (PTSD) (main objective), anxiety, depression, and burnout syndrome (BOS) and their associated factors in ...intensive care unit (ICU) staff workers in the second year of the COVID-19 pandemic.
An international cross-sectional multicenter ICU-based online survey was carried out among the ICU staff workers in 20 ICUs across 3 continents. ICUs staff workers (both caregivers and non-caregivers) were invited to complete PCL-5, HADS, and MBI questionnaires for assessing PTSD, anxiety, depression, and the different components of BOS, respectively. A personal questionnaire was used to isolate independent associated factors with these disorders.
PCL-5, HADS, and MBI questionnaires were completed by 585, 570, and 539 responders, respectively (525 completed all questionnaires). PTSD was diagnosed in 98/585 responders (16.8%). Changing familial environment, being a non-caregiver staff worker, having not being involved in a COVID-19 patient admission, having not been provided with COVID-19-related information were associated with PTSD. Anxiety was reported in 130/570 responders (22.8%). Working in a public hospital, being a woman, being financially impacted, being a non-clinical healthcare staff member, having no theoretical or practical training on individual preventive measures, and fear of managing COVID-19 patients were associated with anxiety. Depression was reported in 50/570 responders (8.8%). Comorbidity at risk of severe COVID-19, working in a public hospital, looking after a child, being a non-caregiver staff member, having no information, and a request for moving from the unit were associated with depression. Having received no information and no adequate training for COVID-19 patient management were associated with all 3 dimensions of BOS.
The present study confirmed that ICU staff workers, whether they treated COVID-19 patients or not, have a substantial prevalence of psychological disorders.
Etomidate and ketamine are used during induction of anesthesia in high-risk patients. However, their effects on action potential (AP) variables and ischemia/reperfusion-induced arrhythmias and ...conduction blocks are unknown.
Guinea pig right ventricular muscle strips were mounted in a 5-mL double chamber bath with the strips separated into two zones by an impermeable latex membrane. One-half (normal zone) was exposed to normal perfusate while the other half (altered zone) was exposed to hypoxia, hyperkalemia, acidosis, and lack of glucose. AP variables were recorded continuously in the normal and altered zones. Spontaneous arrhythmias and conduction blocks were noted. Etomidate (10(-7), 10(-6), and 10(-5) M) and ketamine (10(-6), 10(-5), and 10(-4) M) were superfused into the bath throughout the experiment and the electrophysiologic effects compared with the control group.
We found that under control conditions, etomidate and ketamine did not modify resting membrane potential, maximal upstroke velocity, AP amplitude, or AP duration at 90% of repolarization (APD90). Ketamine (10(-4) M), but not weaker concentrations and none of the concentration of etomidate, reversed the ischemia-induced shortening of APD90 and APD dispersion. Etomidate and ketamine did not modify the occurrence of conduction block during simulated ischemia. In contrast, ketamine (25% at 10(-6) M, 13% at 10(-5) M, and 13% at 10(-4) M vs 90% in the control group, P < 0.05) but not etomidate (38% at 10(-7) M, 63% at 10(-6) M, and 63% at 10(-5) M vs 90% in the control group, NS) decreased the incidence of reperfusion-induced spontaneous arrhythmias.
In guinea pig myocardium, our data suggest that ketamine, in clinically relevant concentrations, decreases ischemia-induced AP shortening and spontaneous reperfusion-induced ventricular arrhythmias. Further study is required to precisely determine the effect of etomidate on reperfusion-induced arrhythmias.
Anesthesia in the elderly Mézière, Anthony; Paillaud, Elena; Plaud, Benoît
La Presse médicale (1983)
42, Številka:
2
Journal Article
Recenzirano
A growing number of old or very old patients benefits from a surgical procedure. Age is an independent risk factor of postoperative mortality and postoperative complications including cognitive ...dysfunction. The choice of anesthetic technique does not significantly modify this risk. Preventive strategies and preoperative procedures can be implemented. A multidisciplinary management involving all care providers around the patient is essential to reduce the risk of dependence after surgery which is higher in this population. Early postoperative rehabilitation is recommended in the elderly to improve the prognosis.
BACKGROUNDDosage guidelines for muscle relaxants are based on dose-response studies, normally performed after several minutes of stable nitrous oxide (N2O)-opioid anesthesia. However, relaxants are ...used immediately after induction of anesthesia. The study was designed to determine the influence of the duration of anesthesia and N2O on the onset time at the adductor pollicis (AP) and the corrugator supercilii (CS) muscles of maximum neuromuscular blockade after mivacurium.
METHODSAfter institutional approval and informed consent, patients were randomly allocated into three groups. Anesthesia was induced with alfentanil and propofol. Group A (n = 10) received mivacurium (0.1 mg/kg) immediately after loss of consciousness. Groups B (n = 10) and C (n = 10) received mivacurium after 15 min of anesthesia with propofol alone (B) or propofol with N2O (C). The evoked response to train-of-four stimulation was measured by acceleromyography at the AP and the CS.
RESULTSMaximum neuromuscular blockade (%T1, median range) was significantly less in group A than in groups B and C (P < 0.001) at both the AP (81 47–90; 90 35–100; 100 93–100, respectively) and the CS (19 5–63; 68 61–100; 89 72–100, respectively). Maximum neuromuscular blockade was less in group B than in group C (P < 0.001) at the AP. Onset time of maximum neuromuscular blockade was not different between groups but was shorter at the CS than at the AP.
CONCLUSIONSDuration of anesthesia and N2O before mivacurium injection affect intensity of neuromuscular blockade but not onset time. Neuromuscular blockade obtained at the AP after several minutes of stable anesthesia with N2O is greater than immediately after induction. This explains in part the discrepancy between the measured ED95 and the intubating dose.
Contracting muscle emits sounds. The purpose of this study was to compare the time course of muscular paralysis at the adductor pollicis muscle (AP) with use of acoustic myography and ...mechanomyography.
Thirteen elective surgery patients, American Society of Anesthesiologists physical status I, received rocuronium (0.6 mg/kg intravenously) as a bolus dose during general anesthesia. Force of AP was measured with use of a strain gauge, and sounds were recorded simultaneously with use of a small condenser microphone fixed on the palmar surface of the hand over the AP. Supramaximal stimulation was applied to the ulnar nerve at 0.1 Hz for 45-60 min. In seven patients, the response to train-of-four stimulation was also recorded during recovery.
Force and sounds both were equally sensitive in measuring maximum block. The relation between sound and force was curvilinear, with good agreement near 0 and 100% and acoustic response exceeding mechanical response at intermediate levels of block. The acoustic signal had a slower onset and a faster recovery than the force response. The fade response of sound to train-of-four stimulation also recovered faster than that of force.
Acoustic myography is an alternative method to monitor muscular paralysis that is easy to set up and applicable to most superficial muscles. However, the time course of relaxation at AP using acoustic myography differs from the time course of force relaxation. Therefore, these two methods are not equivalent when applied to AP.
Sevoflurane has anti-inflammatory proprieties and short lasting effects making it of interest for procedural sedation in critically ill patients. We evaluated the pharmacokinetics of sevoflurane and ...metabolites in severely ill burn patients and controls. The secondary objective was to assess potential kidney injury.
Prospective interventional study in a burn and a surgical intensive care unit; 24 mechanically ventilated critically ill patients (12 burns, 12 controls) were included. The sevoflurane was administered with an expired fraction target of 2% during short-term procedural sedation. Plasma concentrations of sevoflurane, hexafluoroisopropanolol (HFIP) and free fluoride ions were recorded at different times. Kinetic Pro (Wgroupe, France) was used for pharmacokinetic analysis. Kidney injury was assessed with neutrophil gelatinase-associated lipocalin (NGAL).
The mean total burn surface area was 36±11%. The average plasma concentration of sevoflurane was 70.4±37.5mg·L−1 in burns and 57.2±28.1mg·L−1 in controls at the end of the procedure (P=0.58). The volume of distribution was higher (46.8±7.2 vs 22.2±2.50L, P<0.001), and the drug half-life longer in burns (1.19±0.28h vs 0.65±0.04h, P<0.0001). Free metabolite HFIP was higher in burns. Plasma fluoride was not different between burns and controls. NGAL did not rise after procedures.
We observed an increased volume of distribution, slower elimination rate, and altered metabolism of sevoflurane in burn patients compared to controls. Repeated use for procedural sedation in burn patients needs further evaluation. No renal toxicity was detected.
ClinicalTrials.gov Identifier NCT02048683.
To compare, over a 48-hr follow-up period, the analgesia and side-effects of patient controlled iv analgesia (PCA) with morphine alone vs combined intrathecal and PCA morphine (IT+PCA) in patients ...undergoing major abdominal surgery.
Sixty adult patients undergoing abdominal surgery for cancer were randomly allocated to receive preoperative IT (0.3 or 0.4 mg) plus postoperative PCA morphine or postoperative PCA morphine alone. Postoperative analgesia was tested at rest and while coughing on a visual analogue pain scale and morphine consumption was recorded. Patients' satisfaction, arterial oxygen saturation, respiratory rate, episodes of nausea, vomiting and pruritus were also noted.
Analgesia at rest and while coughing was significantly better in the IT+PCA morphine group (rest: P = 0.01; coughing: P = 0.005) on the first postoperative day only. IT+PCA morphine constantly provided adequate analgesia during this period. Morphine consumption was lower in the IT+PCA morphine group during this period also (IT+PCA: 9 (17) vs PCA: 40 (26); mg of morphine, mean (SD), P = 0.0001). No difference was found in pain relief and morphine consumption between the groups on the second postoperative day. Nausea and vomiting were more frequent with IT+PCA morphine on the first postoperative day. No respiratory depression occurred in either group. Satisfaction was high in both groups.
IT+PCA morphine improves patient comfort constantly during the first postoperative day after major abdominal surgery. However, after the first postoperative day, IT+PCA morphine provides no additional benefit.
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