The anesthetic approach to repeated cesarean sections: A prospective cohort study.

Objective: Each repeat cesarean section (CS) potentially adds surgical complexity. The determination of appropriate anesthesia strategy to meet the surgical challenge is of crucial importance for the maternal and neonatal outcome. Study design: This prospective cohort study was conducted from 1-Jan-2021 to 31-Dec-2021 at a single large obstetric centre of all repeat CS. We compared the characteristics and the appropriateness of the anesthesia techniques for low-order repeat CS (LOR-CS) (1 or 2 previous CS) and high order repat CS (HOR-CS) group (3 or more repeat CS). Results: During the study period, 1057 parturients met the study entry criteria, with 821 parturients in the LOR-CS group and 236 parturients in the HOR-CS group. The use of spinal anesthesia was more common for HOR-CS 84.3%. Overall surgical time varied between LOR-CS (38 min, 29-49) and HOR-CS (42 min, 31-57) (p = 0.004).The rate of moderate and severe adhesions was relatively high in HOR-CS and the duration of overall surgical time for cases with mild adhesions was 38 min (29-48), for moderate adhesions was 44 min (34.8-56.5), and for severe adhesions was 56 min (44.8-74.3). There was no significant difference in the Estimated Blood Loss (EBL) between LOR-CS and HOR-CS, with values of 653 ± 292 ml vs. 660 ± 285 ml, respectively. Conclusion: Our data indicate that spinal anesthesia, standard monitoring and regular anesthetic setup are safe and suitable for the majority of HOR-CS, except in cases with high suspicion of placental accreta spectrum.

Preoperative clear fluid fasting and endoscopy-measured gastric fluid volume in children.

BACKGROUND: In light of new recommendations to shorten clear fluid fasting time before anesthesia, our study aimed at exploring residual fluid volume in the stomach after different fasting times. We intended to perform direct endoscopic aspiration of stomach contents under vision, as part of routine gastroscopy assessment. Hereby we would be able to quantify true residual gastric fluid volume and acidity in children and measure their correlation with fasting times. METHODS: The study was performed as a single-center, prospective study in pediatric perioperative day care at a university-affiliated tertiary care center. Aspiration of gastric fluid contents was performed in anesthetized children aged 1-18 years undergoing an elective gastroscopy. Recorded data included patient fast time, last meal content, last clear fluid content, and aspirated gastric volume and pH, as well as patient characteristics. RESULTS: We included 253 gastroscopies, performed in 245 children. Mean fasting time for clear fluids was 6.9 h (range 1 h 40 min - 18 h 35 min) (SD 4.5). Mean age was 9.8 years (SD 5.1) and mean body weight was 33.2 kg (SD 18.7). Mean residual gastric volume was 12 mL (0-90) (SD 13.5) or 0.34 mL/kg (SD 0.37) and mean pH was 1.5 (SD 0.9). No significant correlation was observed between clear fluid fasting time and the child's residual gastric fluid volume per kg body weight (r = -.103, p = .1), nor between clear fluid fasting time and the pH of the residual gastric fluid (r = -.07, p = .3). In more than half of the patients the residual gastric volume was less than 10 mL, unrelated to fasting time. CONCLUSIONS: In children undergoing gastroscopy, we could not demonstrate any association between clear fluid fasting time and the child's residual gastric fluid volume per kg body weight. Since we did not see a clinically relevant association between clear fluids fasting time and gastric residual volume, this study may support the recommendation to shorten clear fluids fasting time.

Reduced postoperative pain in patients receiving nociception monitor guided analgesia during elective major abdominal surgery: a randomized, controlled trial.

The Nociception Level index (NOL™) is a multiparameter index, based on artificial intelligence for the monitoring of nociception during anesthesia. We studied the influence of NOL-guided analgesia on postoperative pain scores in patients undergoing major abdominal surgery during sevoflurane/fentanyl anesthesia. This study was designed as a single-center, prospective randomized, controlled study. After Institutional Review Board approval and written informed consent, 75 ASA 1-3 adult patients undergoing major abdominal surgery, were randomized to NOL-guided fentanyl dosing (NOL) or standard care (SOC) and completed the study. The sevoflurane target MAC range was 0.8-1.2. In the NOL-guided group (N = 36), when NOL values were > 25 for at least 1 min, a weight adjusted fentanyl bolus was administered. In the control group (N = 39) fentanyl administration was based on hemodynamic indices and clinician judgement. After surgery, pain, was evaluated using the Numerical Rating Scale (NRS) pain scale, ranging from 0 to 10, at 15 min intervals for 180 min or until patient discharge from the PACU. Median postoperative pain scores reported were 3.0 [interquartile range 0.0-5.0] and 5.0 [3.0-6.0] at 90 min in NOL-guided and control groups respectively (Bootstrap corrected actual difference 1.5, 95% confidence interval 0.4-2.6). There was no difference in postoperative morphine consumption or intraoperative fentanyl consumption. Postoperative pain scores were significantly improved in nociception level index-guided patients. We attribute this to more objective fentanyl dosing when timed to actual nociceptive stimuli during anesthesia, contributing to lower levels of sympathetic activation and surgical stress. Clinicaltrials.gov identifier: NCT03970291 date of registration May 31, 2019.

Intraoperative use of the machine learning-derived nociception level monitor results in less pain in the first 90†min after surgery.

In this pooled analysis of two randomized clinical trials, intraoperative opioid dosing based on the nociception level-index produced less pain compared to standard care with a difference in pain scores in the post-anesthesia care unit of 1.5 (95% CI 0.8-2.2) points on an 11-point scale. The proportion of patients with severe pain was lower by 70%. Severe postoperative pain remains a significant problem and associates with several adverse outcomes. Here, we determined whether the application of a monitor that detects intraoperative nociceptive events, based on machine learning technology, and treatment of such events reduces pain scores in the post-anesthesia care unit (PACU). To that end, we performed a pooled analysis of two trials in adult patients, undergoing elective major abdominal surgery, on the effect of intraoperative nociception level monitor (NOL)-guided fentanyl dosing on PACU pain was performed. Patients received NOL-guided fentanyl dosing or standard care (fentanyl dosing based on hemodynamic parameters). Goal of the intervention was to keep NOL at values that indicated absence of nociception. The primary endpoint of the study was the median pain score obtained in the first 90 min in the PACU. Pain scores were collected at 15 min intervals on an 11-point Likert scale. Data from 125 patients (55 men, 70 women, age range 21-86 years) were analyzed. Sixty-one patients received NOL-guided fentanyl dosing and 64 standard care. Median PACU pain score was 1.5 points (0.8-2.2) lower in the NOL group compared to the standard care; the proportion of patients with severe pain was 70% lower in the NOL group (p = 0.045). The only significant factor associated with increased odds for severe pain was the standard of care compared to NOL treatment (OR 6.0, 95% CI 1.4 -25.9, p = 0.017). The use of a machine learning-based technology to guide opioid dosing during major abdominal surgery resulted in reduced PACU pain scores with less patients in severe pain.

Is Ultrasound-Guided Single-Shot Quadratus Lumborum Block a Viable Alternative to a Caudal Block in Pediatric Urological Surgery?

OBJECTIVE: To review our experience with quadratus lumborum block (QLB) in pediatric urology. MATERIALS AND METHODS: This mixed prospective-retrospective study included 41 patients who received QLB following induction of general anesthesia. Data collected included: the duration of block induction, surgery, hospitalization, postoperative pain score, and the use of rescue analgesia. The results were compared with a matched cohort of patients who received caudal block (CB) during similar surgeries from our retrospectively acquired data registry. RESULTS: There was no difference between the type and length of surgery, weight, sex, and age of the patients between the two groups. The duration of block induction was significantly shorter in the CB group compared with the QLB group (35.6 ± 14.6 vs. 239 ± 33.4 seconds [p < 0.0001]). There was no difference between the groups in pain scores at 1, 4, and 24 hours postoperatively, in the time to first rescue analgesia, or in the postoperative opioid requirements. However, the QLB group required more rescue analgesia compared with CB group (p = 0.016). Finally, no differences were found in the use of rescue analgesics at home, pain record behavior, and overall satisfaction. CONCLUSION: Our data show that QLB might serve as a viable alternative to CB in pediatric urological surgery.

Outcome of Peripartum Anesthesia in Women with Valvular Disease.

OBJECTIVE: Maternal heart disease is one of the major causes for mortality among parturients. In our study, we surveyed 220 patients with different valvular disorders who gave birth in our medical center in the years 2012-2018. The aim of this study was to characterize various valvular pathologies and compare the results of different anesthetic approaches. METHODS: In this retrospective study, the computerized system and file archive were searched for maternal valvular pathologies according to the International Classification of Diseases, Ninth Revision (ICD-9). The women included in the study were defined as American Society of Anesthesiology (ASA)-II or more, who suffer from valvular heart disease. RESULTS: The most common pathology was mitral valve regurgitation (57.73% of all cardiac patients). Most women were defined as having mild insufficiency, and 82.68% had normal vaginal delivery. In 17.3% of patients who had cesarean section, the main type of anesthesia was neuraxial anesthesia (95.45%). The second most common pathology was tricuspid valve regurgitation (22.73%). Most patients (78%) had normal vaginal delivery, and epidural analgesia was used in 64.1%. A minority of cardiac patients in our study were patients with stenotic heart diseases, such as aortic stenosis, mitral stenosis and pulmonic stenosis (8.18%, 4.55%, and 1.36%, respectively). No complications were observed in the peripartum period. CONCLUSION: The use of regional anesthesia is recommended for all valvular pathologies without exception, as we observed no cases in which the severity of cardiac condition had not allowed the use of various types of regional anesthesia, for surgery or vaginal delivery.

Use of Caudal Analgesia Supplemented with Low Dose of Morphine in Children Who Undergo Renal Surgery.

INTRODUCTION: To test the efficacy and safety of caudal anesthesia (CA) supplemented by low dose morphine in children who undergo renal surgery. MATERIALS AND METHODS: Forty patients aged 2 months-14 years were enrolled and randomly divided into two groups of 20 patients each: Group A (bupivacaine 0.2% with fentanyl); Group B (bupivacaine with morphine). The duration of surgery and hospitalization time were recorded. Postoperative pain score was measured by Face Legs Activity Cry Consolability scale and Wong-Baker Faces scale for those who are older. Overall use of rescue analgesics was calculated. RESULTS: There was no statistical difference in the length of surgery, incidence of pruritus, postoperative nausea, vomiting and urinary retention between the two groups. However the postoperative opioid requirements were significantly higher in Group A 1.03 ± 0.9 mg/kg compared to Group B, in which only one patient required opioid therapy (p < 0.0001). Moreover the need for non-opioid rescue analgesic was higher in Group A, (36 ± 5.7 mg/kg of paracetamol) compared to morphine CA group there only 26 ± 3.6 mg/kg required during first 24 h of the postoperative period (p = 0.0312). The Face Legs Activity Cry Consolability pain score (1, 4, and 24 h after surgery) and Wong-Baker Faces scale were significantly higher in Group A. The hospitalization period was shorter in the CA morphine group, but the difference did not reach statistical significance. None developed hemodynamic instability or respiratory depression. CONCLUSIONS: Our data show that CA supplemented with low dose morphine provides a longer duration of analgesia without significant side-effects in children undergoing renal surgery.

Activation of Adenosine Triphosphate-regulated Potassium Channels during Reperfusion Restores Isoflurane Postconditioning-induced Cardiac Protection in Acutely Hyperglycemic Rabbits.

BACKGROUND: Hyperglycemia is known to inhibit myocardial anesthetic postconditioning. The authors tested whether activation of adenosine triphosphate-regulated potassium (KATP) channels would restore anesthetic postconditioning during acute hyperglycemia. METHODS: Rabbits subjected to 40-min myocardial ischemia and 3-h reperfusion (ischemia-reperfusion [I/R]) were assigned to groups (n = 10 in each group) with or without isoflurane postconditioning (2.1% for 5 min) in the presence or absence of hyperglycemia and/or the KATP channel agonist diazoxide. Creatine kinase MB fraction and infarct size were measured. Phosphorylated protein kinase B (Akt) and endothelial nitric oxide synthase (eNOS) were assessed. Oxidative stress was evaluated by measuring malondialdehyde, and apoptosis was assessed by dUTP nick-end labeling and activated caspase-3. RESULTS: Postconditioning significantly reduced myocardial infarct size (26 ± 4% in the isoflurane [ISO] group vs. 53 ± 2% in the I/R group; P = 0.007); whereas, hyperglycemia inhibited this effect (infarct size: 47 ± 2%, P = 0.02 vs. the ISO group). Phosphorylated and eNOS levels increased, whereas malondialdehyde and myocardial apoptosis were significantly lower after isoflurane postconditioning compared with I/R. These effects were inhibited by acute hyperglycemia. Diazoxide restored the protective effect of isoflurane in the hyperglycemic animals (infarct size: 29 ± 2%; P = 0.01 vs. the I/R group), reduced malondialdehyde levels and myocardial apoptosis, but did not affect the expression of phosphorylated Akt or eNOS. CONCLUSIONS: KATP channel activation restored anesthetic postconditioning-induced myocardial protection under acute hyperglycemia. This effect occurred without increasing Akt or eNOS phosphorylation, suggesting that KATP channels are located downstream to Akt and eNOS in the pathway of isoflurane-induced myocardial postconditioning.

Anesthesiologists' ability in calculating weight-based concentrations for pediatric drug infusions: an observational study.

STUDY OBJECTIVES: To assess the ability of anesthesiologists to calculate weight-specific drug concentrations for continuous drug administration in children, and to evaluate the acceptance of an inhouse-developed, computer-based application for calculating drug infusions for pediatric cardiac surgery. DESIGN: Observational study. SETTING: Anesthesiology department of a tertiary-care medical center in Israel. PARTICIPANTS: 45 anesthesiology department staff members (attendings and residents). MEASUREMENTS: Anesthesiologists were asked to calculate the weight-based amount of drug and the corresponding amount in mL to be drawn from a standard vial and added to a 50-mL syringe in order to reach an infusion rate, where 1 mL/hr corresponds to 1 µg x kg(-1) x min(-1). The time it took to reach the result was measured. Staff members were also asked to rate the user-friendliness and usability of the program. MAIN RESULTS: 41 of the original 42 participants returned the completed questionnaire. Only 6 (15%) of 41 anesthesiologists provided all the correct answers. The mean calculation time required was 205 (±53) seconds. There was no difference in success rate between attendings and residents. Incorrect calculations ranged from a drug concentration 50 times too low up to 56 times too high. Most staff members believed that the computer-based application to perform these calculations reduced errors (65%) and workload (81%), and improved patient treatment (71%). This application was rated as very user-friendly. CONCLUSIONS: Anesthesiologists have difficulty calculating pediatric drug concentrations for continuous drug infusions. The correct calculations are time-consuming. Incorrect calculations may lead to dangerously high or low doses. A computer-based application to calculate drug concentrations was rated as very useful and user-friendly.

Anesthetic considerations for high order cesarean sections: a prospective cohort study.

BACKGROUND: In a previous retrospective study we demonstrated that perioperative complications occurred in a minority of high order repeat cesarean sections (HOR-C/S). In this prospective study we compared the incidence of complications in patients who have had four or more cesarean sections to those that had three or less. METHODS: This was a prospective, observational cohort study of parturients undergoing C/S at a single tertiary care hospital over a 1 year period. We compared the incidence of conversion from regional to general anesthesia, duration of surgery and incidence of major blood loss in HOR-C/S to control. RESULTS: We studied a total of 831 parturients, 129 underwent HOR-C/S. The incidence of conversion from regional to general anesthesia was similar in both groups (RR = 0.97, 95% CI 0.2, 4.3). The median duration of surgery was 40 min (range 10-145 min) in the HOR-C/S group and 30 min (range 10-150 min) in the control group (p < 0.001). The incidence of prolonged surgery was increased in the HOR-C/S group (RR = 3.6, 95% CI 2.4, 5.4). The incidence of intraoperative blood transfusion was higher in the HOR-C/S group (RR = 3.4, 95% CI 1.1, 10.2). CONCLUSIONS: Patients who have HOR-C/S are more likely to have prolonged surgery and require blood transfusion than controls. However, in our population, this was not associated with an increased incidence of conversion from regional to general anesthesia. Provided causes of severe hemorrhage such as abnormal placentation have been ruled out, HOR-C/S is not an absolute contraindication to regional block.

Patterns of use of perioperative angiotensin-converting enzyme inhibitors in coronary artery bypass graft surgery with cardiopulmonary bypass: effects on in-hospital morbidity and mortality.

BACKGROUND: Despite proven benefit in ambulatory patients with ischemic heart disease, the pattern of use of angiotensin-converting enzyme inhibitors (ACEIs) in coronary artery bypass graft surgery has been erratic and controversial. METHODS AND RESULTS: This is a prospective observational study of 4224 patients undergoing coronary artery bypass graft surgery. The cohort included 1838 patients receiving ACEI therapy before surgery and 2386 (56.5%) without ACEI exposure. Postoperatively, the pattern of ACEI use yielded 4 groups: continuation, 915 (21.7%); withdrawal, 923 (21.8%); addition, 343 (8.1%); and no ACEI, 2043 (48.4%). Continuous treatment with ACEI versus no ACEI was associated with substantive reductions of risk of nonfatal events (adjusted odds ratio for the composite outcome, 0.69; 95% confidence interval, 0.52-0.91; P=0.009) and a cardiovascular event (odds ratio, 0.64; 95% confidence interval, 0.46-0.88; P=0.006). Addition of ACEI de novo postoperatively compared with no ACEI therapy was also associated with a significant reduction of risk of composite outcome (odds ratio, 0.56; 95% confidence interval, 0.38-0.84; P=0.004) and a cardiovascular event (odds ratio, 0.63; 95% confidence interval, 0.40-0.97; P=0.04). On the other hand, continuous treatment of ACEI versus withdrawal of ACEI was associated with decreased risk of the composite outcome (odds ratio, 0.50; 95% confidence interval, 0.38-0.66; P<0.001), as well as a decrease in cardiac and renal events (P<0.001 and P=0.005, respectively). No differences in in-hospital mortality and cerebral events were noted. CONCLUSIONS: Our study suggests that withdrawal of ACEI treatment after coronary artery bypass graft surgery is associated with nonfatal in-hospital ischemic events. Furthermore, continuation of ACEI or de novo ACEI therapy early after cardiac surgery is associated with improved in-hospital outcomes.

Hyperglycemia inhibits anesthetic-induced postconditioning in the rabbit heart via modulation of phosphatidylinositol-3-kinase/Akt and endothelial nitric oxide synthase signaling.

Hyperglycemia is known to inhibit ischemic and anesthetic preconditioning. We tested whether hyperglycemia inhibits anesthetic postconditioning with isoflurane and whether this effect is mediated via phosphatidylinositol-3-kinase/Akt and nitric oxide signaling. New Zealand white rabbits subjected to 40 minutes of myocardial ischemia, followed by 3 hours of reperfusion were assigned to the following groups: ischemia and reperfusion (I/R), isoflurane (1 minimal alveolar concentration) postconditioning, and isoflurane postconditioning with hyperglycemia (15% dextrose in water infusion). A control group of hyperglycemia + I/R was also included. Levels of MB fraction of creatine kinase (CK-MB) were assessed as an indicator of myocardial damage, and infarct size was evaluated. Akt, iNOS, and endothelial nitric oxide synthase (eNOS) expression was assessed by immunoblotting. Determination of nitrite and nitrate levels in the myocardium was also performed. Isoflurane postconditioning reduced infarct size compared with the I/R group: 25% +/- 4% versus 49% +/- 5% (P < 0.01). CK-MB concentrations in the postconditioned animals (124% +/- 14% above baseline levels) were lower than those in the I/R group (236% +/- 9% above baseline levels; P < 0.01). Hyperglycemia inhibited the cardioprotective effect of isoflurane: myocardial infarction size was 46% +/- 4% and CK-MB increased to 241% +/- 11% above baseline. Phosphorylated Akt and eNOS protein expression increased after isoflurane postconditioning compared with the I/R group. These effects were also inhibited by hyperglycemia. iNOS expression, however, did not change significantly within the various experimental groups. There were increased tissue levels of nitrite and nitrate (NO(x)) in the postconditioning group. This was also blocked by hyperglycemia. Our results suggest that hyperglycemia inhibits cardioprotection provided by isoflurane postconditioning. This effect seems to be mediated via modulation Akt and eNOS.

Pediatric sedation/anesthesia outside the operating room.

PURPOSE OF REVIEW: The demand of procedures performed on children outside the operating room setting often exceeds the capacity of anesthesia services. The number of children requiring sedation outside the traditional operating room is rapidly approaching the number of children requiring anesthesia in the operating room. We address some of the major issues and controversies in this continuously evolving field. RECENT FINDINGS: Pediatric sedation continues to be a challenging field. Recently, the Society of Pediatric Sedation has been created. In the last year, important issues have been raised among pediatric sedation providers, keeping on feeding the debate within all the recognized experts. Why worry about nihil per os status? Is bispectral index useful as a sedation monitor? Should there be standards for simulation-based training of nonanesthesiologists for delivery of sedation? Is propofol well tolerated? Is dexmedetomidine a good choice for painful procedures? What is the role of etomidate? SUMMARY: A standard approach (adequate preparation, clinical assessment of the child, fasting as required and right sedation plan) is mandatory to provide safety and efficiency. Sedation is a continuum, and it can be easy to advance from one level to the next and even reach a state of general anesthesia. Newer modalities such as end-tidal CO2 and, maybe, bispectral index monitoring are indeed enhancing the safety of procedural sedation and analgesia.

Myocardial metabolism altered by ischemic preconditioning and enflurane in off-pump coronary artery surgery.

OBJECTIVE: During off-pump coronary artery bypass (OPCAB) surgery, the heart is subjected to ischemia and reperfusion. The authors hypothesized that the volatile anesthetics are as effective as ischemic preconditioning (IPC) in preserving myocardial function during off-pump cardiac surgery, and this effect is because of multiple mechanisms of action. Therefore, the effects of enflurane with its calcium inhibition and antioxidative properties were compared with mechanical IPC in preserving myocardial cellular markers. DESIGN: A prospective, randomized, controlled, and partly blinded study. SETTING: A tertiary care university hospital. PARTICIPANTS: Twenty-five patients undergoing elective single-graft OPCAB surgery. INTERVENTIONS: Patients were randomized into 3 groups: (1) control (n = 8), (2) a single 5-minute ischemia/reperfusion interval of IPC before coronary occlusion (n = 9), and (3) 1.6% enflurane anesthesia 15 minutes before and during graft attachment (n = 8). Arterial and coronary sinus venous blood were analyzed for biochemical indices of ischemia and hydroxyl radical generation. MEASUREMENTS AND MAIN RESULTS: Although the hemodynamic changes were small, myocardial lactate production in the control group increased by 120%, whereas in the enflurane group it decreased significantly (p < 0.01) compared with the control and IPC groups. Oxygen utilization in the control group was 44% higher (p < 0.03), and there was also a larger release of the hydroxyl radical-dependent adduct 2,3-dihydroxybenzoic acid (225% increase, p < 0.05) compared with both study groups. During reperfusion, initial anterior wall hypokinesis by TEE was observed, with slow recovery during reperfusion compared with early recovery in both study groups. CONCLUSIONS: Coronary occlusion during OPCAB surgery results in increased production of ischemia-related metabolic products. The application of methods such as IPC or volatile anesthesia appears to reduce the metabolic deficit, free-radical production, and physiologic changes.

Flumazenil mimics whereas midazolam abolishes ischemic preconditioning in a rabbit heart model of ischemia-reperfusion.

BACKGROUND: The goal of the current study was to assess the effects of flumazenil, a benzodiazepine receptor antagonist, in limiting infarct size and in reducing hydroxyl free radical production. METHODS: After intravenous salicylate (100 mg/kg) administration, rabbits were subjected to 40 min of regional myocardial ischemia and 2 h of reperfusion. In one group, flumazenil (0.05 mg/kg) and, in another, midazolam (0.05 mg/kg) was administered 15 min before 40 min of ischemia. Ischemic preconditioning (IP) was elicited by 5 min of ischemia followed by 10 min of reperfusion (before the 40-min ischemia period). In two other groups, midazolam was added to flumazenil and IP. Infarct size was determined using triphenyl tetrazolium chloride staining. The authors quantified the hydroxyl-mediated conversion of salicylate to its 2,3- and 2,5-dihydroxybenzoate derivatives during reperfusion by high-performance liquid chromatography coupled with electrochemical detection. Results are expressed as mean +/- SEM. RESULTS: Flumazenil, like IP, significantly decreased infarct size (23 +/- 4 and 22 +/- 5%, respectively, vs. 57 +/- 6% in control group; P < 0.01). Midazolam inhibited the effects of flumazenil and IP. Flumazenil and IP significantly limited the increase in the normalized concentrations of 2,3- and 2,5-dihydroxybenzoic acids. With midazolam, however, the increase was comparable to that of the control group. 5-Hydroxydecanoate, a selective mitochondrial adenosine triphosphate-sensitive K channel blocker, given with flumazenil, abolished the protection obtained with the latter. CONCLUSIONS: Flumazenil mimics preconditioning to decrease infarct size and hydroxyl radical production during reperfusion. Midazolam, however, abolishes these effects. Blockade of benzodiazepine receptors is upstream to the mitochondrial adenosine triphosphate-sensitive K channels in the preconditioning cascade.

Volatile anesthetic preconditioning attenuates myocardial apoptosis in rabbits after regional ischemia and reperfusion via Akt signaling and modulation of Bcl-2 family proteins.

We tested whether isoflurane preconditioning inhibits cardiomyocyte apoptosis and evaluated the role of the phosphatidylinositol-3-kinase (PI3K)/Akt pathway in anesthetic preconditioning and determined whether PI3K/Akt signaling modulates the expression of pro- and antiapoptotic proteins in anesthetic preconditioning. Six-month-old New Zealand rabbits subjected to 40 min of myocardial ischemia followed by 180 min of reperfusion were assigned to the following groups: ischemia-reperfusion (I/R), isoflurane preconditioning and isoflurane plus PI3K inhibitors, wortmannin and 2-(4-morpholinyl)-8-phenyl-4H-l-benzopyran-4-one (LY294002) (0.6 and 0.3 mg/kg i.v., respectively). Sham-operated, wortmannin+I/R, wortmannin+sham, LY294002+I/R, and LY294002+sham groups were also included. Infarct size was assessed by triphenyltetrazolium chloride staining. Apoptosis was evaluated by terminal deoxynucleotidyl transferase-mediated dUTP nick-end labeling and activated caspase-3 assays. Akt phosphorylation, Bax, Bcl-2, Bad, and phosphorylated Bad (phospho-Bad) expression was assessed by immunoblotting. Isoflurane preconditioning reduced infarct size compared with the I/R group: 22+/-4 versus 41+/-5% (p<0.05). The percentage of apoptotic cells decreased in the isoflurane group (3.8+/-1.2%) compared with the I/R group (12.4+/-1.6%; p<0.05). These results were also confirmed by the activated caspase-3 assay. Wortmannin and LY294002 inhibited the effects of isoflurane. Myocardial infarction increased to 44+/-3 and 45+/-2% and the percentage of apoptotic cells was 11.9+/-2.1 and 11.7+/-3.3%, respectively. Akt phosphorylation and Bcl-2 and phospho-Bad expression increased after isoflurane preconditioning, whereas Bax expression decreased. These effects were inhibited by wortmannin and LY294002. The data indicate that isoflurane preconditioning reduces infarct size and myocardial apoptosis after I/R. Activation of PI3K and modulation of the expression of pro- and antiapoptotic proteins may play a role in isoflurane-induced myocardial protection.

Ischemic preconditioning decreases the reperfusion-related formation of hydroxyl radicals in a rabbit model of regional myocardial ischemia and reperfusion: the role of K(ATP) channels.

The objective of this study was to assess the effects of ischemic preconditioning (IP) on hydroxyl free radical production in an in vivo rabbit model of regional ischemia and reperfusion. Another goal was to determine whether K(ATP) channels are involved in these effects. The hearts of anesthetized and mechanically ventilated New Zealand White rabbits were exposed through a left thoracotomy. After i.v. salicylate (100 mg/kg) administration, all animals underwent a 30-min stabilization period followed by 40 min of regional ischemia and 2 h of reperfusion. In the IP group, IP was elicited by 5 min of ischemia followed by 10 min of reperfusion (prior to the 40-min ischemia period). Glibenclamide, a K(ATP) channel blocker, was administered prior to the preconditioning stimulus. Infarct size was measured by 2,3,5-triphenyl tetrazolium chloride (TTC) staining. We quantified the hydroxyl-mediated conversion of salicylate to its 2,3 and 2,5-dihydroxybenzoate derivatives during reperfusion by high performance liquid chromatography coupled with electro-chemical detection.IP was evidenced by reduced infarct size compared to control animals: 22% vs. 58%, respectively. Glibenclamide inhibited this cardioprotective effect and infarct size was 53%. IP limited the increase in 2,3 and 2,5-dihydroxybenzoic acid to 24.3 and 23.8% above baseline, respectively. Glibenclamide abrogated this effect and the increase in 2,3 and 2,5-dihydroxybenzoic acid was 94.3 and 85% above baseline levels, respectively, similar to the increase in the control group. We demonstrated that IP decreased the formation of hydroxyl radicals during reperfusion. The fact that glibenclamide inhibited this effect, indicates that K(ATP) channels play a key role in this cardioprotective effect of IP.

Platelet-derived microparticles induce angiogenesis and stimulate post-ischemic revascularization.

OBJECTIVE: Platelet activation is accompanied by the release of microparticles. However, little is known about the role of platelet-derived microparticles (PMP) in the regulation of angiogenesis and related clinical situations. The aim of our study was to evaluate the effect of PMP on angiogenesis and to analyze its mechanisms. METHODS: Both in vitro (rat aortic ring model, cell invasion test) and in vivo (agarose bead transplantation, artificial cardiac ischemia in Sabra rats) approaches were used in the study. RESULTS: A dose-dependent pro-angiogenic effect of PMP was observed in the rat aortic ring model. This effect could be eliminated by inhibition of VEGF, bFGF, and PDGF, but not heparanase. PMP exerted their effect via PI 3-kinase, Src kinase, and ERK, whereas protein kinase C and p38 were not involved. Moreover, PMP induced invasion of endothelial cells through a layer of matrigel. This effect was mediated by VEGF, heparanase, and PDGF, but not bFGF. Furthermore, PMP induced angiogenesis in an in vivo model in which agarose beads containing PMP were transplanted subcutaneously into mice. In addition, the effect of PMP on angiogenesis was evaluated in the model of in vivo chronic myocardial ischemia in rats. Ischemia induced a decrease in the number of functioning capillaries (34+/-21.5 vs. 157+/-42.0 per view field), but their amount increased after injection of PMP into the myocarium (97+/-27.3; p<0.001 vs. ischemia without PMP). CONCLUSIONS: PMP induce angiogenesis both in vitro and in vivo. Injection of PMP into the ischemic myocardium might improve the process of revascularization after chronic ischemia.

Emergency airway management with a laryngeal mask airway in a patient placed in the prone position.

Accidental extubation of a patient while placed in the prone position is a life-threatening, anesthesia-related complication. We describe a case of accidental extubation of the trachea during spine surgery in a patient placed in the prone position. We successfully managed this emergent problem by inserting a Laryngeal Mask Airway while maintaining the patient in the same position.