Resumo em Inglês:

Abstract Introduction: Postoperative nausea and vomiting is still a common complication. Serotonin receptor antagonists are commonly used in clinical practice for antiemetic prophylaxis. Interin-dividual variations in drug response, including single nucleotide polymorphisms, are related to pharmacokinetic and pharmacodynamic changes in these drugs and may lead to a poor therapeutic response. This study aimed to evaluate the influence of CYP2D6 isoenzyme and ABCB1 gene polymorphisms on the frequency of postoperative nausea and vomiting with the use of ondansetron or palonosetron. Methods: A randomized, double-blind clinical trial including 82 women aged 60 years or over undergoing laparoscopic cholecystectomy was conducted. Patients were randomized to receive either ondansetron or palonosetron for postoperative nausea and vomiting prophylaxis. DNA was extracted from saliva. Genetic polymorphisms were analyzed by real-time polymerase chain reaction. The following polymorphisms were analyzed: rs3892097 C/T, rs1128503 A/G, rs16947A/G, rs1065852 A/G, rs1045642 A/G, rs2032582 C/A, and rs20325821 C/A. Results: Overall, vomiting, and severe nausea occurred in 22.5% and 57.5% of patients, respectively. In the palonosetron group, patients with the GG genotype (rs16947 A/G) experienced more severe nausea (p = 0.043). In the ondansetron group, patients with the M genotype (rs16947 A/G) presented mild nausea (p = 0.034), and those with the AA genotype (rs1065852 A/G) experienced more vomiting (p = 0.034). Conclusion: A low antiemetic response was observed with ondansetron in the presence of the AA genotype (rs16947 A/G) and the AA genotype (rs1065852 A/G), and a low therapeutic response was found with palonosetron in the presence of the GG genotype (rs16947 A/G) in laparoscopic cholecystectomy. Register: ClinicalTrials.gov.

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Abstract Background: Most cardiac surgery patients experience postoperative anemia. Delirium and Atrial Fibrillation (AF) are common and independent predictors of morbidity and mortality. Few reports examine their association with postoperative anemia. This study aims to quantify the association between anemia and these outcomes in patients undergoing cardiac surgery. Methods: This post-hoc analysis of the DECADE randomized controlled trial ran at six academic US hospitals. Patients aged 18–85 years with heart rate > 50 bpm undergoing cardiac surgery who had daily hemoglobin measurements in the first 5 Postoperative Days (POD) were included. Delirium was assessed twice daily with the Confusion Assessment Method for the ICU (CAM – ICU), preceded by the Richmond Agitation and Sedation Scale, with patients excluded from assessment if sedated. Patients had daily hemoglobin measurements, continuous cardiac monitoring plus twice-daily 12-lead electrocardiograms, up to POD4. AF was diagnosed by clinicians blinded to hemoglobin levels. Results: Five hundred and eighty-five patients were included. Mean postoperative hemoglobin Hazard Ratio (HR): 0.99 (95% CI 0.83, 1.19; p = 0.94) per 1 g.dL–1 hemoglobin decrease. 197 (34%) developed AF, mainly on POD = 2.3. Estimated HR = 1.04 (95% CI 0.93, 1.17; p = 0.51) per 1 g.dL–1 hemoglobin decrease. Conclusions: Most patients undergoing major cardiac surgery were anemic in the postoperative phase. AF and delirium occurred in 34% and 12% of patients, respectively, but neither were significantly correlated with postoperative hemoglobin.

Resumo em Inglês:

Abstract Background: Systemic inflammatory responses mimicking infectious complications are often present in surgical patients. Methods: The objective was to assess the association between withholding early antimicrobial therapy while investigating alternative diagnoses and worse outcomes in nonseptic patients with suspected nosocomial infection in a retrospective cohort of critically ill surgical patients. The initiation of antibiotic therapy within 24 h of the suspicion of infection was defined as the Early Empirical Antibiotic strategy (EEA) group and the initiation after 24 h of suspicion or not prescribed was defined as the Conservative Antibiotic strategy (CA) group. Primary outcome was composite: death, sepsis, or septic shock within 14 days. Main exclusion criteria were sepsis or an evident source of infection at inclusion. Results: Three hundred and forty patients were eligible for inclusion (74% trauma patients). Age, sex, reason for hospital admission, SAPS3 score, SOFA score, and use of vasopressors or mechanical ventilation were not different between the groups. Within 14 days of inclusion, 100% (130/130) of EEA patients received antibiotics compared to 57% (120/210) of CA patients. After adjusting for confounding variables, there was no association between primary outcome and the groups. In a post hoc subgroup analysis including only patients with a posteriori confirmed infection (by microbiological cultures), delay in initiation of adequate antimicrobial therapy was independently associated with the primary outcome (Odds Ratio = 1.19 per day of delay; 95% CI 1.05–1.37). Conclusions: Withholding early empiric antibiotic therapy was not associated with progression of organ dysfunction within 14 days in nonseptic surgical patients with suspected nosocomial infection without an obvious source.

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Abstract Background: Patients diagnosed with Obstructive Sleep Apnea (OSA) syndrome have a tendency towards hypoventilation, hypoxia, and hypercarbia in the perioperative period. This study hypothesized that the Oxygen Reserve Index (ORi) could predict possible hypoxia and determine difficult airways in patients at risk for OSA, as determined by the STOP-Bang questionnaire. Methods: This prospective study included adult patients undergoing elective surgery under general anesthesia with endotracheal intubation, divided into two groups: low risk (0–2 points) and high risk (3–8 points) based on their STOP-Bang questionnaire results. The primary outcome measure was the highest ORi value reached during preoxygenation and the time to reach this value. Data were recorded at four time points: before preoxygenation (T1), end of preoxygenation (T2), end of mask ventilation (T3), and end of intubation (T4), as well as partial oxygen pressure values in T1, T2, and T4. The secondary outcome measures were the grading scale for mask ventilation, Cormack-Lehane score, tonsil dimensions, use of a stylet, and application of the burp maneuver during intubation. Results: In the high-risk group, preoperative peripheral oxygen saturation values, the highest ORi value reached in preoxygenation, and ORi values at T3 and T4 times were lower, and the time to reach the highest ORi value was longer (p < 0.05). Conclusion: Using ORi in patients with OSA may be useful in evaluating oxygenation, and since difficult airway is more common, ORi monitoring will better manage possible hypoxic conditions.

Resumo em Inglês:

Abstract Background: Pneumonia occurs in about 20% of trauma patients with pulmonary contusions. This study aims to evaluate the association between empirical antibiotic therapy and nosocomial pneumonia in this population. Methods: Retrospective cohort of adult patients admitted to a trauma-surgical ICU. The Antibiotic Therapy Group (ATG) was defined by intravenous antibiotic use for more than 48 h starting on hospital admission, while the Conservative Group (CG) was determined by antibiotic use no longer than 48 h. Primary outcome was microbiologically documented nosocomial pneumonia within 14 days after hospital admission. Logistic regression was used to estimate the association between group allocation and primary outcome. Exploratory analyses evaluating the association between resistant strains in pneumonia and antibiotic use were performed. Results: The study included 177 patients with chest trauma and pulmonary contusion on CTscan. ATG were more severely ill than CG, as shown by higher Injury Severity Score, SAPS3, SOFA score, higher rates, and longer duration of mechanical ventilation. In the multivariate analysis, ATG was associated with a lower incidence of primary outcome (OR = 0.25, 95% CI 0.09-0.64; p < 0.01). Similar results were found in the sensitivity analysis with another set of variables. However, each day of antibiotic use was associated with an increased risk of pneumonia by resistant bacteria (OR = 1.18 per day, 95% CI 1.05-1.36; p < 0.01). Conclusions: Empiric antibiotic therapy was independently associated with lower incidence of nosocomial pneumonia in critically ill patients with pulmonary contusion. However, each day of antibiotic use was associated with increased resistant strains in infected patients.

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Abstract Background: Alarms alert healthcare professionals of deviations from normal/physiologic status. However, alarm fatigue may occur when their high pitch and diversity overwhelm clinicians, possibly leading to alarms being disabled, paused, and/or ignored. We aimed to determine whether a staff educational program on customizing alarm settings of bedside monitors may decrease inconsistent alarms in the Post-Anesthesia Care Unit (PACU). Methods: This is a prospective, analytic, quantitative, pragmatic, open-label, single-arm study. The outcome was evaluated on PACU admission before (P1) and after (P2) the implementation of the educational program. The heart rate, blood pressure, and oxygen saturation alarms were selected for clinical consistency. Results: A total of 260 patients were included and 344 clinical alarms collected, with 270 (78.4%) before (P1), and 74 (21.6%) after (P2) the intervention. Among the 270 alarms in P1, 45.2% were inconsistent (i.e., false alarms), compared to 9.4% of the 74 in P2. Patients with consistent alarms occurred in 30% in the P1 and 27% in the P2 (p = 0.08). Patients with inconsistent alarms occurred in 25.4% in the P1 and in 3.8% in the P2. Ignored consistent alarms were reduced from 21.5% to 2.6% (p = 0.004) in the P2 group. The educational program was a protective factor for the inconsistent clinical alarm (OR = 0.11 [95% CI 0.04-0.3]; p < 0.001) after adjustments for age, gender, and ASA physical status. Conclusion: Customizing alarm settings on PACU admission proved to be a protective factor against inconsistent alarm notifications of multiparametric monitors.

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Abstract Background: The Iowa Satisfaction with Anesthesia Scale (ISAS) was developed to assess the satisfaction of patients undergoing sedation with monitored anesthesia care. This study aimed to cross-culturally adapt the ISAS instrument and evaluate the acceptability, validity, and reliability of the proposed Brazilian version (ISAS-Br). Methods: The cross-cultural adaptation process involved translation, synthesis, back-translation, expert committee review, pre-testing, and final review of the ISAS-Br. A cross-sectional study was conducted, involving 127 adult individuals undergoing ambulatory surgeries with moderate/deep sedation. The acceptability, reliability, and construct validity of the scale were assessed. Results: The cross-cultural adaptation process did not require significant changes to the final version of the scale. The ISAS-Br demonstrated excellent acceptability, with a completion rate of 99% and an average completion time of 4.6 minutes. Exploratory factor analysis revealed three factors: emotional well-being, physical comfort, and anxiety relief, with respective composite reliability coefficient values of 0.874, 0.580, and 0.428. The test-retest reliability of the ISAS-Br, measured by the intraclass correlation coefficient, was 0.67 (95% confidence interval [95% CI] 0.42 to 0.83), and the Bland-Altman plot showed satisfactory agreement between the measurements. Conclusion: The proposed Brazilian version of the ISAS underwent successful cross-cultural adaptation according to international standards. It demonstrated good acceptability and reliability, regarding the assessment of temporal stability. However, the ISAS-Br exhibited low internal consistency for some factors, indicating that this instrument lacks sensitivity to assess the satisfaction of deeply sedated patients. Further studies are necessary to explore the hypotheses raised based on the knowledge of its psychometric properties.

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Abstract Background: Myelomeningocele (MMC) is a neural tube defect disease. Antenatal repair of fetal MMC is an alternative to postnatal repair. Many agents can be used as tocolytics during the in utero fetal repair such as β2-agonists and oxytocin receptor antagonists, with possible maternal and fetal repercussions. This study aims to compare maternal arterial blood gas analysis between terbutaline or atosiban, as tocolytic agents, during intrauterine MMC repair. Methods: Retrospective cohort study. Patients were divided into two groups depending on the main tocolytic agent used during intrauterine MMC repair: atosiban (16) or terbutaline (9). Maternal arterial blood gas samples were analyzed on three moments: post induction (baseline, before the start of tocolysis), before extubation, and two hours after the end of the surgery. Results: Twenty-five patients were included and assessed. Before extubation, the terbutaline group showed lower arterial pH (7.347 ± 0.05 vs. 7.396 ± 0.02 for atosiban, p = 0.006) and higher arterial lactate (28.33 ± 12.76 mg.dL–1 vs. 13.06 ± 6.35 mg.dL–1, for atosiban, p = 0.001) levels. Conclusions: Patients who received terbutaline had more acidosis and higher levels of lactate, compared to those who received atosiban, during intrauterine fetal MMC repair.

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Abstract Introduction: Cardiac arrest or arrhythmia caused by bupivacaine may be refractory to treatment. Apelin has been reported to directly increase the frequency of spontaneous activation and the propagation of action potentials, ultimately promoting cardiac contractility. This study aimed to investigate the effects of apelin-13 in reversing cardiac suppression induced by bupivacaine in rats. Methods: A rat model of cardiac suppression was established by a 3-min continuous intravenous infusion of bupivacaine at the rate of 5 mg.kg−1.min−1, and serial doses of apelin-13 (50, 150 and 450 μg.kg−1) were administered to rescue cardiac suppression to identify its dose-response relationship. We used F13A, an inhibitor of Angiotensin Receptor-Like 1 (APJ), and Protein Kinase C (PKC) inhibitor chelerythrine to reverse the effects of apelin-13. Moreover, the protein expressions of PKC, Nav1.5, and APJ in ventricular tissues were measured using Western blotting and immunofluorescence assay. Results: Compared to the control rats, the rats subjected to continuous intravenous administration of bupivacaine had impaired hemodynamic stability. Administration of apelin-13, in a dose-dependent manner, significantly improved hemodynamic parameters in rats with bupivacaine-induced cardiac suppression (p < 0.05), and apelin-13 treatment also significantly upregulated the protein expressions of p-PKC and Nav1.5 (p < 0.05), these effects were abrogated by F13A or chelerythrine (p < 0.05). Conclusion: Exogenous apelin-13, at least in part, activates the PKC signaling pathway through the apelin/APJ system to improve cardiac function in a rat model of bupivacaine-induced cardiac suppression.

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Abstract Background: This study aimed to investigate the analgesic impact of S(+)-ketamine on pain behavior and synovial inflammation in an osteoarthritis (OA) model. Methods: Animals were grouped as follows: OA-Saline (n = 24) and OA-Ketamine (n = 24), OA induced via intra-articular sodium monoiodoacetate (MIA); a Non-OA group (n = 24) served as the control. On the 7th day post OA induction, animals received either saline or S(+)-ketamine (0.5 mg.kg–1). Behavioral and histopathological assessments were conducted up to day 28. Results: S(+)-ketamine reduced allodynia from day 7 to 28 and hyperalgesia from day 10 to 28. It notably alleviated weight distribution deficits from day 10 until the end of the study. Significant walking improvement was observed on day 14 in S(+)-ketamine-treated rats. Starting on day 14, OA groups showed grip force decline, which was countered by S(+)-ketamine on day 21. However, S(+)-ketamine did not diminish synovial inflammation. Conclusion: Low Intra-articular (IA) doses of S(+)-ketamine reduced MIA-induced OA pain but did not reverse synovial histopathological changes. IRB approval number: 23115 012030/2009-05.

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Abstract Background: Acute Kidney Injury (AKI) is a common complication after cardiac surgery and has been associated with poor outcomes. Dexmedetomidine (DEX) has been shown to confer direct renoprotection based on some animal and clinical studies, but data from other trials came to the opposite conclusion following cardiac surgery. This meta-analysis was conducted to evaluate the effects of perioperative DEX administration on the occurrence of AKI and the outcomes after cardiac surgery. Methods: We searched databases including EMBASE, PubMed, and Cochrane CENTRAL for Randomized Controlled Trials (RCTs) focused on DEX for AKI in adult patients after cardiac surgery. The primary outcome was incidence of AKI. Secondary outcomes were Mechanical Ventilation (MV) duration, Intensive Care Unit (ICU) Length Of Stay (LOS), hospital LOS and mortality. Results: Fifteen trials enrolling 2907 study patients were collected in the meta-analyses. Compared with controls, DEX reduced the incidence of postoperative AKI (Odds Ratio [OR = 0.66]; 95% Confidence Interval [95% CI 0.48–0.91]; p = 0.01), and there was no significant difference between groups in postoperative mortality (OR = 0.63; 95% CI 0.32–1.26; p = 0.19), MV duration (Weighted Mean Difference [WMD = -0.44]; 95% CI -1.50–0.63; p = 0.42), ICU LOS (WMD = -1.19; 95% CI -2.89-0.51; p = 0.17), and hospital LOS (WMD = -0.31; 95% CI -0.76–0.15; p = 0.19). Conclusions: Perioperative DEX reduced the incidence of postoperative AKI in adult patients undergoing cardiac surgery. No significant decrease existed in mortality, MV duration, ICU LOS and hospital LOS owing to DEX administration.