Neuroprotective effect of erythropoietin on anesthesia-induced neurotoxicity through the modulation of autophagy in Caenorhabditis elegans

Background  The anti-oxidative, anti-inflammatory, and anti-apoptotic effects of erythropoietin may provide neuroprotective effects. Erythropoietin also modulates autophagy signaling that may play a role in anesthesia-induced neurotoxicity (AIN). Herein, we investigated whether AIN can be attenuated by the neuroprotective effect of erythropoietin in the Caenorhabditis elegans (C. elegans). Methods  Synchronized worms were divided into the control, Iso, EPO, and EPO-Iso groups. The chemotaxis index (CI) was evaluated when they reached the young adult stage. The lgg-1::GFP-positive puncta per seam cell were used to determine the autophagic events. The erythropoietin-mediated pathway of autophagy was determined by measuring the genetic expression level of let-363, bec-1, atg-7, atg-5, and lgg-3. Results  Increased lgg-1::GFP puncta were observed in the Iso, EPO, and EPO-Iso groups. In the Iso group, only the let-363 level decreased significantly as compared to that in the control group (P = 0.009). bec-1 (P < 0.001), atg-5 (P = 0.012), and lgg-3 (P < 0.001) were expressed significantly more in the EPO-Iso group than in the Iso groups. Repeated isoflurane exposure during development decreased the CI. Erythropoietin could restore the decreased CI by isoflurane significantly in the EPO-Iso group. Conclusions  Erythropoietin showed neuroprotective effects against AIN and modulated the autophagic pathway in C. elegans. This experimental evidence of erythropoietin-related neuroprotection against AIN may be correlated with the induced autophagic degradation process that was sufficient for handling enhanced autophagy induction in erythropoietin-treated worms.

Comparison of analgesic effects between programmed intermittent epidural boluses and continuous epidural infusion after cesarean section: a randomized controlled study

Background  This study aimed to compare the analgesic effects of programmed intermittent epidural boluses (PIEB) and continuous epidural infusion (CEI) for postoperative analgesia after elective cesarean section (CS). Methods  Seventy-four women who underwent elective CS were randomized to receive either PIEB or CEI. The PIEB group received 4 ml-intermittent boluses of 0.11% ropivacaine every hour at a rate of 120 ml/h. The CEI group received a constant rate of 4 ml/h of 0.11% ropivacaine. The primary outcome was the pain score at rest at 36 h after CS. Secondary outcomes included the pain scores during mobilization, time-weighted pain scores, the incidence of motor blockade, and complications-related epidural analgesia during 36 h after CS. Results  The pain score at rest at 36 h after CS was significantly lower in the PIEB group compared with that in the CEI group (3.0 vs. 0.0; median difference: 2, 95% CI [1, 2], P < 0.001). The mean time-weighted pain scores at rest and during mobilizations were also significantly lower in the PIEB group than in the CEI group (pain at rest; mean difference [MD]: 37.5, 95% CI [24.6, 50.4], P < 0.001/pain during mobilization; MD: 56.6, 95% CI [39.8, 73.5], P < 0.001). The incidence of motor blockade was significantly reduced in the PIEB group compared with that in the CEI group (P < 0.001). Conclusions  PIEB provides superior analgesia with less motor blockade than CEI in postpartum women after CS, without any apparent adverse events.

The minimum effective concentration (MEC90) of bupivacaine for an ultrasound-guided suprainguinal fascia iliaca compartment block for analgesia in knee surgery: a dose-finding study

Background  In recent years, the suprainguinal fascia iliaca compartment block (SFICB) has become more common in clinical practice. This assessor-blinded dose-finding study aimed to determine the minimum effective concentration (MEC90, MEC95) of bupivacaine for a single-injection SFICB in patients undergoing arthroscopic anterior cruciate ligament repair. Methods  This prospective study was conducted at a tertiary hospital (postoperative recovery room and ward). The SFICB was performed as a postsurgical intervention after spinal anesthesia. Seventy patients were allocated using the biased-coin design up-and-down sequential method. The ultrasound-guided SFICB was performed using different bupivacaine concentrations, and standard multimodal analgesia was administered to all patients. Block success was defined as the absence of pain or presence of only tactile sensation during the pinprick test conducted on the anterior and lateral regions of the mid-thigh six hours postoperatively. Results  According to isotonic regression and bootstrap CIs, the MEC90 value of bupivacaine for a successful SFICB was 0.123% (95% CI [0.098, 0.191]) and the MEC95 value was 0.188% (95% CI [0.113, 0.223]). Conclusions  Our study showed that the MEC90 and MEC95 values for bupivacaine administered via an SFICB for analgesia were 0.123% and 0.188%, respectively. One advantage of using lower concentrations of bupivacaine is the associated reduction in quadriceps weakness.

Comparison of lung aeration loss in open abdominal oncologic surgeries after ventilation with electrical impedance tomography-guided PEEP versus conventional PEEP: a pilot feasibility study

Background  Existing literature lacks high-quality evidence regarding the ideal intraoperative positive end-expiratory pressure (PEEP) to minimize postoperative pulmonary complications (PPCs). We hypothesized that applying individualized PEEP derived from electrical impedance tomography would reduce the severity of postoperative lung aeration loss, deterioration in oxygenation, and PPC incidence. Methods  A pilot feasibility study was conducted on 36 patients who underwent open abdominal oncologic surgery. The patients were randomized to receive individualized PEEP or conventional PEEP at 4 cmH2O. The primary outcome was the impact of individualized PEEP on changes in the modified lung ultrasound score (MLUS) derived from preoperative and postoperative lung ultrasonography. A higher MLUS indicated greater lung aeration loss. The secondary outcomes were the PaO2/FiO2 ratio and PPC incidence. Results  A significant increase in the postoperative MLUS (12.0 ± 3.6 vs 7.9 ± 2.1, P < 0.001) and a significant difference between the postoperative and preoperative MLUS values (7.0 ± 3.3 vs 3.0 ± 1.6, P < 0.001) were found in the conventional PEEP group, indicating increased lung aeration loss. In the conventional PEEP group, the intraoperative PaO2/FiO2 ratios were significantly lower, but not the postoperative ratios. The PPC incidence was not significantly different between the groups. Post-hoc analysis showed the increase in lung aeration loss and deterioration of intraoperative oxygenation correlated with the deviation from the individualized PEEP. Conclusions  Individualized PEEP appears to protect against lung aeration loss and intraoperative oxygenation deterioration. The advantage was greater in patients whose individualized PEEP deviated more from the conventional PEEP.

Efficacy of intraoperative blood salvage and autotransfusion in living-donor liver transplantation: a retrospective cohort study

Background  Liver transplantation (LT) may be associated with massive blood loss and the need for allogeneic blood transfusion. Intraoperative blood salvage autotransfusion (IBSA) can reduce the need for allogeneic blood transfusion. This study aimed to investigate the effectiveness of blood salvage in LT. Methods  Among 355 adult patients who underwent elective living-donor LT between January 1, 2019, and December 31, 2022, 59 recipients without advanced hepatocellular carcinoma received IBSA using Cell Saver (CS group). Based on sex, age, model for end-stage liver disease (MELD) score, preoperative laboratory results, and other factors, 118 of the 296 recipients who did not undergo IBSA were matched using propensity score (non-CS group). The primary outcome was the amount of intraoperative allogenic red blood cell (RBC) transfusion. Comparisons were made between the two groups regarding the amount of other blood components transfused and postoperative laboratory findings. Results  The transfused allogeneic RBC for the CS group was significantly lower than that of the non-CS group (1,506.0 vs. 1,957.5 ml, P = 0.026). No significant differences in the transfused total fresh frozen plasma, platelets, cryoprecipitate, and estimated blood loss were observed between the two groups. The postoperative allogeneic RBC transfusion was significantly lower in the CS group than in the non-CS group (1,500.0 vs. 2,100.0 ml, P = 0.039). No significant differences in postoperative laboratory findings were observed at postoperative day 1 and discharge. Conclusions  Using IBSA during LT can effectively reduce the need for perioperative allogeneic blood transfusions without causing subsequent coagulopathy.

Comparison of effects of telmisartan versus valsartan on post-induction hypotension during noncardiac surgery: a prospective observational study

Background  Telmisartan is considered more potent than valsartan. Hemodynamic response during anesthesia induction may be influenced by anti-hypertension (HTN) medication. The present study compared the effect of anti-HTN medications on post-induction hypotension during noncardiac surgeries. Methods  This observational study standardized the anesthetic regimen across patients, with hypotension defined as mean blood pressure (BP) of less than 65 mmHg. The hemodynamic changes within 5 min before and after endotracheal intubation, and within 10 min before and after surgical incision were measured. Transthoracic echocardiographic evaluation of the left ventricle (LV) during anesthesia induction was performed. The primary endpoint was the decline in mean BP after anesthetic administration in telmisartan and valsartan groups. Multivariate logistic regression analysis was used to identify predictors of post-induction hypotension. Results  Data from 157 patients undergoing noncardiac surgery were analyzed. No significant differences were found in mean BP decline between the two groups during anesthesia induction. Hemodynamic changes and LV ejection fraction (EF) during anesthesia induction were similar between the groups. Age and preoperative initial mean BP in operation room (OR) were associated with post-induction hypotension in both groups. Conclusions  The angiotensin receptor blocker (ARB) type did not influence post-induction hypotension during anesthesia induction. Age and preoperative initial mean BP in OR were associated with post-induction hypotension in patients taking ARBs.

Intraoperative pediatric electroencephalography monitoring: an updated review

Intraoperative electroencephalography (EEG) monitoring under pediatric anesthesia has begun to attract increasing interest, driven by the availability of pediatric-specific EEG monitors and the realization that traditional dosing methods based on patient movement or changes in hemodynamic response often lead to imprecise dosing, especially in younger infants who may experience adverse events (e.g., hypotension) due to excess anesthesia. EEG directly measures the effects of anesthetics on the brain, which is the target end-organ responsible for inducing loss of consciousness. Over the past ten years, research on anesthesia and computational neuroscience has improved our understanding of intraoperative pediatric EEG monitoring and expanded the utility of EEG in clinical practice. We now have better insights into neurodevelopmental changes in the developing pediatric brain, functional connectivity, the use of non-proprietary EEG parameters to guide anesthetic dosing, epileptiform EEG changes during induction, EEG changes from spinal/regional anesthesia, EEG discontinuity, and the use of EEG to improve clinical outcomes. This review article summarizes the recent literature on EEG monitoring in perioperative pediatric anesthesia, highlighting several of the topics mentioned above.

Comparison of preemptive and preventive intravenous acetaminophen on opioid consumption in pediatrics undergoing posterior spinal fusion surgery: a randomized controlled trial

Background  Posterior spinal fusion (PSF), commonly used for adolescent idiopathic scoliosis (AIS), causes severe postoperative pain. Intravenous (IV) administration of acetaminophen has shown promise for opioid-sparing analgesia; however, its analgesic effect and optimal timing for its standard use remain unclear. Our study aimed to evaluate the analgesic effect and optimal timing of IV acetaminophen administration in pediatric and adolescent patients undergoing PSF and requiring adequate pain control. Methods  This prospective, randomized, triple-blind trial was conducted in patients aged 11–20 undergoing PSF. Participants were randomized into three groups: the preemptive group (received IV acetaminophen 15 mg/kg after anesthetic induction/before surgical incision), the preventive group (received IV acetaminophen 15 mg/kg at the end of surgery/before skin closure), and the placebo group. The primary outcome was cumulative opioid consumption during the first 24 h postoperatively. Results  Among the 99 enrolled patients, the mean ± standard deviation (SD) amount of opioid consumption during the postoperative 24 h was 60.66 ± 23.84, 52.23 ± 22.43, and 66.70 ± 23.01 mg in the preemptive, preventive, and placebo groups, respectively (overall P = 0.043). A post hoc analysis revealed that the preventive group had significantly lower opioid consumption than the placebo group (P = 0.013). However, no significant differences between the groups were observed for the secondary outcomes. Conclusions  The preventive administration of scheduled IV acetaminophen reduces cumulative opioid consumption without increasing the incidence of drug-induced adverse events in pediatric and adolescent patients undergoing PSF.

Alternatives to the P value: connotations of significance

The statistical significance of a clinical trial analysis result is determined by a mathematical calculation and probability based on null hypothesis significance testing. However, statistical significance does not always align with meaningful clinical effects; thus, assigning clinical relevance to statistical significance is unreasonable. A statistical result incorporating a clinically meaningful difference is a better approach to present statistical significance. Thus, the minimal clinically important difference (MCID), which requires integrating minimum clinically relevant changes from the early stages of research design, has been introduced. As a follow-up to the previous statistical round article on P values, confidence intervals, and effect sizes, in this article, we present hands-on examples of MCID and various effect sizes and discuss the terms statistical significance and clinical relevance, including cautions regarding their use.

Perioperative management of patients with cardiac implantable electronic devices

The use of cardiac implantable electronic devices (CIEDs) has increased significantly in recent years. Consequently, more patients with CIEDs will undergo surgery during their lifetime, and thus the involvement of anesthesiologists in the perioperative management of CIEDs is increasing. With ongoing advancements in technology, many types of CIEDs have been developed, including permanent pacemakers, leadless pacemakers, implantable cardioverter defibrillators, cardiac resynchronization therapy-pacemakers/defibrillators, and implantable loop recorders. The functioning of CIEDs exposed to an electromagnetic field can be affected by electromagnetic interference, potential sources of which can be found in the operating room. Thus, to prevent potential adverse events caused by electromagnetic interference in the operating room, anesthesiologists must have knowledge of CIEDs and be able to identify each type. This review focuses on the perioperative management of patients with CIEDs, including indications for CIED implantation to determine the baseline cardiovascular status of patients; concerns associated with CIEDs before and during surgery; perioperative management of CIEDs, including magnet application and device reprogramming; and additional perioperative provisions for patients with CIEDs. As issues such as variations in programming capabilities and responses to magnet application according to device can be challenging, this review provides essential information for the safe perioperative management of patients with CIEDs.