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"Anesthetics."
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Anesthetics
Provides the history of anesthetics, with details on the different kinds of anesthetics, how anesthetics work, when and where they're used, and their complications and side effects.
Book
Anesthetics influence the incidence of acute kidney injury following valvular heart surgery
Propofol has been shown to provide protection against renal ischemia/reperfusion injury experimentally, but clinical evidence is lacking. Here we studied the effect of propofol anesthesia on the occurrence of acute kidney injury following heart surgery with cardiopulmonary bypass. One hundred and twelve patients who underwent valvular heart surgery were randomized to receive either propofol or sevoflurane anesthesia, both with sufentanil. Using Acute Kidney Injury Network criteria, significantly fewer patients developed acute kidney injury postoperatively in the propofol group compared with the sevoflurane group (6 compared with 21 patients). The incidence of severe renal dysfunction was significantly higher in the sevoflurane group compared with the propofol group (5 compared with none). The postoperative cystatin C was significantly lower in the propofol group at 24 and 48h. Serum interleukin-6 at 6h after aorta cross-clamp removal, C-reactive protein at postoperative day 1, and segmented neutrophil counts at postoperative day 3 were also significantly lower in the propofol group. Thus, propofol anesthesia significantly reduced the incidence and severity of acute kidney injury in patients undergoing valvular heart surgery with cardiopulmonary bypass compared with sevoflurane. This beneficial effect of propofol may be related to its ability to attenuate the perioperative increase in proinflammatory mediators.
Journal Article
Long-term sedation in intensive care unit: a randomized comparison between inhaled sevoflurane and intravenous propofol or midazolam
Purpose
To evaluate efficacy and adverse events related to inhaled sevoflurane for long-term sedation compared with standard intravenous (IV) sedation with propofol or midazolam.
Methods
Randomized controlled trial. Sixty intensive care unit (ICU) patients expected to require more than 24 h sedation were randomly assigned to one of three groups: group S, inhaled sevoflurane; group P, IV propofol; group M, IV midazolam. All patients also received IV remifentanil for goal-directed sedation (Ramsay scale and pain score) until extubation or for a maximum of 96 h. Primary end points were wake-up times and extubation delay from termination of sedative administration. Proportion of time within Ramsay score 3–4, IV morphine consumption at 24 h post extubation, hallucination episodes after end of sedation, adverse events, inorganic fluoride plasma levels, and ambient sevoflurane concentrations were recorded.
Results
Forty-seven patients were analyzed. Wake-up time and extubation delay were significantly (
P
< 0.01) shorter in group S (18.6 ± 11.8 and 33.6 ± 13.1 min) than in group P (91.3 ± 35.2 and 326.11 ± 360.2 min) or M (260.2 ± 150.2 and 599.6 ± 586.6 min). Proportion of time within desired interval of sedation score was comparable between groups. Morphine consumption during the 24 h following extubation was lower in group S than in groups P and M. Four hallucination episodes were reported in group P, five in group M, and none in group S (
P
= 0.04). No hepatic or renal adverse events were reported. Mean plasma fluoride value was 82 μmol l
−1
(range 12–220 μmol l
−1
), and mean ambient sevoflurane concentration was 0.3 ± 0.1 ppm.
Conclusions
Long-term inhaled sevoflurane sedation seems to be a safe and effective alternative to IV propofol or midazolam. It decreases wake-up and extubation times, and post extubation morphine consumption, and increases awakening quality.
Journal Article
Effect of intravenous versus inhaled anesthetics on blood-brain barrier dysfunction and neuroinflammation in elderly patients undergoing major surgery: study protocol of a randomized controlled trial
Background
Postoperative cognitive dysfunction (POCD) is one of the major complications after surgery, with devastating clinical outcomes. Although POCD is a condition with a multifactorial pathophysiology, blood-brain barrier (BBB) dysfunction and neuronal injury have been shown to play a critical role, especially in the elderly. Previous studies have demonstrated that the choice of anesthetics affect BBB permeability and neuroinflammation. However, most studies are carried out on animals, with limited research undertaken on humans. Therefore, we will compare the effect of intravenous anesthetics and inhaled anesthetics on BBB dysfunction and the change of inflammatory markers after surgery.
Methods
One hundred and fifty-four patients who are 60 years of age or older undergoing major surgery for more than 2 h will be randomly allocated to two anesthetics groups (intravenous, inhaled) in a 1:1 ratio. In the intravenous anesthetics group (group P), propofol will be infused with a target-controlled infusion (TCI) system throughout the entire surgery. In the inhaled anesthetics group (group G), bolus injection of propofol will be administered for loss of consciousness, and simultaneously sevoflurane will be initiated for the maintenance of anesthesia. The primary outcome is the change in serum S100 calcium binding protein β (S100β) at four time points: before induction of anesthesia, at the end of surgery, 4 h after surgery, postoperative day 1. Secondary outcomes include changes in the inflammatory markers, serum interleukin (IL)-6, IL-8, tumor necrosis factor (TNF)-α, and C-reactive protein; the incidence of delirium; and the change in the cognitive function between groups. In patients pre-scheduled for postoperative intensive care unit admission, the cerebrospinal fluid/serum albumin quotient (Qalb) between the two groups will be compared before and after surgery, and change in inflammatory markers in serum and CSF will be analyzed in relation to the Qalb.
Discussion
The current study will compare the effect of intravenous versus inhaled anesthetics on blood-brain barrier permeability and, as a result, the difference in neuroinflammation in elderly patients. Also, the study results will provide additional information to develop intraoperative anesthetic strategies to reduce POCD.
Trial registration
The trial was prospectively registered at Clinical Trials protocol registration with identifier 2310-117-126 on April 9, 2024.
Journal Article
Effect of propofol, sevoflurane, and isoflurane on postoperative cognitive dysfunction following laparoscopic cholecystectomy in elderly patients: A randomized controlled trial
To compare the incidence of postoperative cognitive dysfunction (POCD) in elderly surgical patients (>60years) receiving different anesthetics (propofol, sevoflurane, or isoflurane) and to identify potential biomarkers of POCD in this patient population.
Prospective, randomized, double-blind clinical trial.
University-affiliated teaching hospital.
One hundred and fifty elderly patients scheduled for laparoscopic cholecystectomy.
Elderly patients undergoing laparoscopic cholecystectomy were randomly assigned to receive propofol, sevoflurane, or isoflurane anesthesia. Measurements: Cognitive function was assessed using neuropsychological tests at baseline (1day before surgery [D0]), and on postoperative day 1 (D1) and day 3 (D3). Plasma S-100β and Aβ1–40 protein, IL-1β, IL-6 and TNF-α concentrations were assessed before induction of anesthesia (T0), after extubation (T1), and 1h (T2) and 24h (T3) postoperatively.
The incidence of POCD was significantly lower in the propofol group compared to the isoflurane group and the sevoflurane group at D1 and D3 (propofol vs. isoflurane: D1 and D3, P<0.001; propofol vs. sevoflurane: D1, P=0.012; D3, P=0.013). The incidence of POCD was significantly lower in the sevoflurane group compared to the isoflurane group at D1 (P=0.041), but not at D3. Postoperatively, plasma S-100β and Aβ1–40 protein, IL-1β, IL-6, and TNF-α concentrations were significantly decreased in the propofol group compared to the isoflurane group.
Propofol anesthesia may be an option for elderly surgical patients.
•Postoperative cognitive dysfunction is commonly occurred in elderly.•Anesthesia impaired the cognitive function.•Propofol had little effect then inhaled anesthetics.
Journal Article
Shared structural mechanisms of general anaesthetics and benzodiazepines
Most general anaesthetics and classical benzodiazepine drugs act through positive modulation of γ-aminobutyric acid type A (GABA
A
) receptors to dampen neuronal activity in the brain
1
–
5
. However, direct structural information on the mechanisms of general anaesthetics at their physiological receptor sites is lacking. Here we present cryo-electron microscopy structures of GABA
A
receptors bound to intravenous anaesthetics, benzodiazepines and inhibitory modulators. These structures were solved in a lipidic environment and are complemented by electrophysiology and molecular dynamics simulations. Structures of GABA
A
receptors in complex with the anaesthetics phenobarbital, etomidate and propofol reveal both distinct and common transmembrane binding sites, which are shared in part by the benzodiazepine drug diazepam. Structures in which GABA
A
receptors are bound by benzodiazepine-site ligands identify an additional membrane binding site for diazepam and suggest an allosteric mechanism for anaesthetic reversal by flumazenil. This study provides a foundation for understanding how pharmacologically diverse and clinically essential drugs act through overlapping and distinct mechanisms to potentiate inhibitory signalling in the brain.
Cryo-electron microscopy structures of GABA
A
receptors bound to intravenous anaesthetics and benzodiazepines reveal both common and distinct transmembrane binding sites, and show that the mechanisms of action of anaesthetics partially overlap with those of benzodiazepines.
Journal Article
Comparison of the effect of isoflurane and propofol on liver regeneration after donor hepatectomy - A randomized controlled trial
The biotransformation of inhalational anesthetic agents can result in production of hepatotoxic metabolites, which may potentially impair liver regeneration. Thus, isoflurane and propofol may have differential impacts on liver regeneration after donor hepatectomy.
To compare the regeneration liver volume (RgLV) via computed tomography (CT) volumetry on post-operative day (POD) 14 in isoflurane and propofol groups.
Randomized controlled pilot trial.
Sixty donors, who underwent donor hepatectomy.
Patients were randomized into isoflurane and propofol group using computer generated random number tables. In isoflurane group, anesthesia was maintained with isoflurane 1–2 % in air‑oxygen mixture. In propofol group, anesthesia was maintained with the target-controlled infusion (TCI) of propofol using a TCI system (Perfusor® Space- B. Braun) at a plasma target concentration of 3–6 μg.ml−1. BIS was recorded in all patients.
Liver CT volumetry was assessed at POD 14.
RgLV on POD14 was comparable in two groups [449.3(170) & 437.8 (177.8) cm3, [Mean Difference (MD) -11.904 95 % Confidence Interval(CI) -101.83, 78.03 respectively; p = 0.79].
Administering propofol or isoflurane may not have differential effect on liver regeneration after donor hepatectomy.
•Hepatotoxic metabolites of inhalational anesthetics may impair liver regeneration.•Regeneration after donor hepatectomy were studied between isoflurane and propofol.•Regeneration volume was comparable between the two groups.•Serum bile acid and Stromal cell derived factor-1 were higher in isoflurane group.•Albumin was lower in isoflurane group than propofol group.
Journal Article
Impact of propofol versus desflurane anesthesia on postoperative hepatic and renal functions in infants with living-related liver transplantation: a randomized controlled trial
Background
The effects of anesthetics on liver and kidney functions after infantile living-related liver transplantation (LRLT) are unclear. This study aimed to investigate the effects of propofol-based total intravenous anesthesia (TIVA) or desflurane-based inhalation anesthesia on postoperative liver and kidney functions in infant recipients after LRLT and to evaluate hepatic ischemia–reperfusion injury (HIRI).
Methods
Seventy-six infants with congenital biliary atresia scheduled for LRLT were randomly divided into two anesthesia maintenance groups: group D with continuous inhalation of desflurane and group P with an infusion of propofol. The primary focus was to assess alterations of liver transaminase and serum creatinine (Scr) levels within the first 7 days after surgery. And the peak aminotransferase level within 72 h post-surgery was used as a surrogate marker for HIRI.
Results
There were no differences in preoperative hepatic and renal functions between the two groups. Upon the intensive care unit (ICU) arrival, the levels of aspartate aminotransferase (AST,
P
= 0.001) and alanine aminotransferase (ALT,
P
= 0.005) in group P were significantly lower than those in group D. These changes persisted until the fourth and sixth days after surgery. The peak AST and ALT levels within 72 h after surgery were also lower in group P than in group D (856 (552, 1221) vs. 1468 (732, 1969) U/L,
P
= 0.001 (95% CI: 161–777) and 517 (428, 704) vs. 730 (541, 1100) U/L,
P
= 0.006, (95% CI: 58–366), respectively). Patients in group P had lower levels of Scr upon the ICU arrival and on the first day after surgery, compared to group D (17.8 (15.2, 22.0) vs. 23.0 (20.8, 30.8) μmol/L,
P
< 0.001 (95% CI: 3.0–8.7) and 17.1 (14.9, 21.0) vs. 20.5 (16.5, 25.3) μmol/L,
P
= 0.02 (95% CI: 0.0–5.0) respectively). Moreover, the incidence of severe acute kidney injury was significantly lower in group P compared to that in group D (15.8% vs. 39.5%,
P
= 0.038).
Conclusions
Propofol-based TIVA might improve liver and kidney functions after LRLT in infants and reduce the incidence of serious complications, which may be related to the reduction of HIRI. However, further biomarkers will be necessary to prove these associations.
Journal Article
Effect of ketamine combined with lidocaine in pediatric anesthesia
Background We conducted a randomized clinical trial to determine whether adjunctive lidocaine diminishes the incidence of adverse effects in pediatric patients sedated with ketamine. Methods This case‐control study involved 586 consecutive pediatric patients necessitating anesthesia. Then systolic blood pressure, heart rate, respiratory rate, and blood oxygen saturation were observed. Alanine aminotransferase (ALT), aspartate aminotransferase (AST), urea nitrogen (BUN), and creatinine (Cr) levels were tested. General dose of ketamine, the time of onset and duration of anesthesia and postoperative recovery, anesthesia effect, and adverse reaction were subsequently compared. High‐performance liquid chromatography was employed to detect ketamine concentration at different time points after administration, and the postoperative cognition function was further evaluated. Results Intra‐ and post‐operation, the rising degree of ALT, AST, BUN, and Cr in patients treated with ketamine was higher than those in patients treated with the ketamine‐lidocaine complex. General dose of ketamine, the time of onset and duration of anesthesia, postoperative recovery time, and the incidence rate of adverse reaction in patients treated with ketamine‐lidocaine complex were lower, but the concentration of ketamine was higher compared to the patients treated with ketamine. In patients treated with the ketamine‐lidocaine complex, elimination half‐life of ketamine was prolonged, the area under curve was increased, and the plasma clearance rate was decreased relative to those with ketamine alone. Conclusions Ketamine combined with lidocaine may be beneficial in shortening the onset of anesthesia, promoting postoperative awake, prolonging elimination half‐life, increasing area under curve, and decreasing plasma clearance rate and incidence of adverse reactions.
Journal Article
Postoperative cognitive dysfunction after inhalational anesthesia in elderly patients undergoing major surgery: the influence of anesthetic technique, cerebral injury and systemic inflammation
Background
Elderly patients are reportedly at higher risk of postoperative cognitive dysfunction (POCD) after inhalational anesthesia with sevoflurane. We hypothesized that the incidence of POCD would be higher in elderly patients undergoing major surgery under inhalational rather than intravenous anesthesia. We also measured plasma S-100β protein concentration as a biomarker of central nervous system injury, and plasma interleukin (IL)-6 and tumor necrosis factor (TNF)-α concentrations to judge the contribution of systemic inflammation to POCD.
Methods
Ninety patients aged 65–75 years scheduled for resection of an esophageal carcinoma were randomly assigned to one of three groups (
n
= 30) as follows: a group receiving sevoflurane anesthesia (Group S); a group receiving preoperative methylprednisolone before sevoflurane anesthesia (Group S + MP); and a control group maintained with intravenous propofol (Group C). The mini-mental state examination (MMSE) and Montreal cognitive assessment (MoCA) were used to measure patients’ cognitive function the day before surgery, and on the first, third and seventh postoperative days. The plasma concentrations of TNF-α, IL-6 and S-100β protein were measured 10 min before anesthesia, and on the first, third and seventh postoperative days.
Results
There were no significant differences in the demographic or clinical characteristics, or perioperative hemodynamic status, of the three groups. The MMSE and MoCA scores were significantly lower in Group S than in the propofol control (Group C) and Group S + MP on the first, third and seventh postoperative days (
P
<0.05). Throughout the first postoperative week the plasma concentrations of TNF-α, IL-6, and S-100β protein were significantly elevated in Group S compared with Group C (
P
<0.05), but were significantly lower in Group S + MP than Group S (
P
<0.05).
Conclusions
The incidence of POCD was higher in elderly patients undergoing major surgery under inhalational anesthesia with sevoflurane than those maintained on intravenous propofol, and lower in elderly patients pro-treating with methylprednisolone. Furthermore, we found elevated plasma concentrations of S-100β protein, TNF-α and IL-6 in those receiving sevoflurane anesthesia.
Trial registration
ChiCTR-IOR-15007007
(02-09-2015).
Journal Article