Efeitos do rocurônio,sugamadex e complexo rocurônio‐sugamadex sobre a coagulação em ratos

Background and objectivesSugammadex is an alternative pharmacological drug capable of reversing neuromuscular blockades without the limitations that are presented by anticholinesterase drugs. Coagulation disorders that are related to treatment with sugammadex were reported. The exact mechanism of the effects on coagulation are not fully understood. The objective of this research is to evaluate the effects of rocuronium, sugammadex and the rocuronium‐sugammadex complex on coagulation in an experimental model in rats.MethodsThis is an experimental randomized animal study. Wistar rats were randomly assigned into the following groups: the Control Group; the Ssal Group – 0.5 mL of intravenous saline; the Sugammadex Group – intravenous sugammadex (100 mg.kg^‐1); and the Rocuronium‐Sugammadex Group – intravenous solution with rocuronium (3.75 mg.kg^‐1) and sugammadex (100 mg.kg^‐1). Anesthesia was performed by using isoflurane with controlled ventilation. Coagulation factors were measured 10 minutes after the end of the preoperative preparation and 30 minutes after the administration of the drugs in accordance with the chosen groups.ResultsPlatelet counts, prothrombin times and activated partial thromboplastin times were similar between the groups and between the moments within each group. There were reductions in the plasma fibrinogen levels between sample times 1 and 2 in the Rocuronium‐Sugammadex group (p = 0.035).ConclusionsThe rocuronium‐sugammadex complex promoted reductions in plasma fibrinogen counts, although the levels were still within normal limits.     

The effect of rocuronium, sugammadex, and their combination on cardiac muscle and diaphragmatic skeletal muscle cells

Purpose

Rocuronium has been associated with muscle weakness when administered in prolonged infusions. The effect of sugammadex and rocuronium together on muscle is unknown. In this study, we examined the effects of rocuronium and sugammadex, and the complex formed by these agents, on cardiac and diaphragmatic muscle cells.

Methods

Forty-two Sprague–Dawley male rats were divided into six groups. Group I received only rocuronium at a dose of 1 mg/kg and groups II and III received sugammadex alone at doses of 16 and 96 mg/kg, respectively. Groups IV and V received 1 mg/kg rocuronium plus 16 mg/kg sugammadex and 1 mg/kg rocuronium plus 96 mg/kg sugammadex, respectively. Group six was the control group and received only 0.9 % NaCl without any drug.

Results

Histopathological examination demonstrated that rocuronium and high doses of sugammadex accumulated in both cardiac and diaphragm muscle tissues. We also observed intense edema and degeneration in diaphragmatic and myocardial cells when the rocuronium-sugammadex complex was used. Rocuronium and sugammadex remain in the circulation for a long time and they may cause skeletal muscle myopathy, vacuolization, pyknotic nuclear clumps, and hypertrophy, and weaken the muscle fibers.

Conclusion

Rocuronium, sugammadex, and rocuronium–sugammadex complexes cause histopathological changes and immunoreactivity to calcineurin in muscle cells.     

Postoperative oxygenation assessed by SpO2/FiO2 ratio and respiratory complications after reversal of neuromuscular block with Sugammadex or neostigmine: A retrospective cohort study

Study objectiveResidual neuromuscular block may lead to postoperative muscle weakness, inadequate oxygenation, and other pulmonary complications. Sugammadex may provide more rapid and effective restoration of neuromuscular function than neostigmine. We therefore tested the primary hypothesis that noncardiac surgical patients given sugammadex oxygenate better during initial recovery than those given neostigmine. Secondarily, we tested the hypothesis that patients given sugammadex have fewer pulmonary complications during hospitalization.DesignRetrospective cohort analysis.SettingPostoperative recovery area of a tertiary care hospital.PatientsAdults who had non-cardiothoracic surgery and were given either neostigmine or sugammadex.InterventionsNone.MeasurementsThe primary outcome was the lowest SpO₂/FiO₂ ratio in the post-anesthesia care unit. The secondary outcome was a composite of pulmonary complications.Main resultsAmong 71,457 cases, 10,708 (15%) were given sugammadex and 60,749 (85%) received neostigmine. After propensity weighting, the mean minimum SpO₂/FiO₂ ratio was 301 ± 77 (SD) in patients given sugammadex and 303 ± 71 in those given neostigmine, yielding an estimated difference in means of −3.5 (95% confidence interval: −5.3, −1.7; P = 0.0002). 4.4% of patients given sugammadex and 3.6% of patients given neostigmine had postoperative pulmonary complications (P = 0.0005, number-needed-to-be-exposed =136; 95% CI: 83, 330), with the main contributing components being new bronchospasm or exacerbation of obstructive pulmonary disease.ConclusionsPostoperative minimum SpO₂/FiO₂ ratio during PACU admission was similar after reversal of neuromuscular block by sugammadex and neostigmine. Reversal with sugammadex was associated with more pulmonary complications, but most were minor and of little consequence.     

Efficacy and safety of sugammadex compared to neostigmine for reversal of neuromuscular blockade: a meta-analysis of randomized controlled trials

Background and objectiveSugammadex has been introduced for reversal of rocuronium (or vecuronium)–induced neuromuscular blockade (NMB). Although its efficacy has been established, data are conflicting whether it is safer than neostigmine traditionally used for reversing NMB.DesignMeta-analysis of data about effectiveness and safety of sugammadex compared to neostigmine for reversing NMB in adults was performed using the PRISMA methodology.SettingUniversity medical hospital.MethodsA comprehensive search was conducted using PubMed, Web of Science, and Cochrane Library electronic databases to identify English-language randomized controlled trials. Two reviewers independently selected the trials; extracted data on reversal times, incomplete reversals of NMB, and adverse events (AEs); and assessed the trials' methodological quality and evidence level. Only AEs that were related to study drug by a blinded safety assessor were considered for meta-analysis.PatientsA total of 1384 patients from 13 articles were included in this meta-analysis.Main resultsCompared to neostigmine, sugammadex was faster in reversing NMB (P < .0001) and more likely to be associated with higher train-of-four ratio values at extubation (mean difference, 0.18; 95% confidence interval [CI], 0.14-0.22; P < .0001) and lower risk of postoperative residual curarization after extubation (odds ratio [OR], 0.05; 95% CI, 0.01-0.43; P = .0068). Compared to neostigmine, sugammadex was associated with a significantly lower likelihood of global AEs (OR, 0.47; 95% CI, 0.34-0.66; P < .0001), respiratory AEs (OR, 0.36; 95% CI, 0.14-0.95; P = .0386), cardiovascular AEs (OR, 0.23; 95% CI, 0.08-0.61; P = .0036), and postoperative weakness (OR, 0.45; 95% CI, 0.21-0.97; P = .0409). Sugammadex and neostigmine were associated with a similar likelihood of postoperative nausea and vomiting (OR, 1.23; 95% CI, 0.70-2.15; P = .4719), pain (OR, 1.06; 95% CI, 0.15-7.36; P = .9559), neurologic AEs (OR, 1.47; 95% CI, 0.52-4.17; P = .4699), general AEs (OR, 0.75; 95% CI, 0.47-1.21; P = .2448), and changes in laboratory tests' values (OR, 0.57; 95% CI, 0.18-1.78; P = .3368).ConclusionsResults from this meta-analysis suggest that sugammadex is superior to neostigmine, as it reverses NMB faster and more reliably, with a lower risk of AEs.     

Role of sugammadex in accelerating postoperative discharge: A meta-analysis

Study objectiveSugammadex has been introduced for reversal of neuromuscular blockade (NMB) induced by rocuronium (or vecuronium). Although its efficacy and safety have been established, data are conflicting as to whether it accelerates discharge to the surgical ward compared with neostigmine, which is traditionally used for reversing NMB. The object of this systematic review and meta-analysis was to review the research comparing sugammadex and neostigmine in the context of patient discharge after general anesthesia.DesignSystematic review and meta-analysis.SettingUniversity medical hospital.PatientsFive-hundred eighteen patients from six studies were included.MethodsA comprehensive search was conducted using PubMed, Web of Science, Google Scholar, and Cochrane Library electronic databases to identify randomized controlled trials written in English. Two reviewers independently selected the studies, extracted data regarding postoperative discharge, and assessed the trials' methodological quality and evidence level. Postoperative discharge time was determined from the operating room (OR) to the postanesthesia care unit (PACU) and from the PACU to the surgical ward. This study was conducted using PRISMA methodology.MeasurementsTime to discharge after NMB reversal with sugammadex or neostigmine.Main resultsCompared with neostigmine, sugammadex was associated with a significantly faster discharge from the OR to the PACU (mean difference [MD] = 22.14 min, 95% CI (14.62, 29.67), P < 0.0001, I² = 0%) and from the PACU to the surgical ward (MD = 16.95 min, 95% CI (0.23, 33.67), P = 0.0469, I² = 98.4%). Similarly, discharge-readiness was shorter for sugammadex than for neostigmine from the OR to the PACU (MD = 5.58 min, 95% CI (3.03, 8.14), P ≤ 0.0001, I² = 0%). However, discharge-readiness was similar in both groups for patients moving from the PACU to the surgical ward (MD = − 1.10 min, 95% CI (− 5.69, 3.50), P = 0.6394, I² = 25.3%).ConclusionsResults from this meta-analysis suggest that sugammadex accelerates postoperative discharge of patients after general anesthesia compared with neostigmine.     

Sugammadex efficacy for reversal of rocuronium- and vecuronium-induced neuromuscular blockade: A pooled analysis of 26 studies

Study objectiveTo summarize and compare efficacy of sugammadex with neostigmine or placebo for reversal of rocuronium- or vecuronium-induced neuromuscular blockade (NMB), and to demonstrate consistency of sugammadex results across various patient populations.DesignPooled analysis on data from 26 multicenter, randomized, Phase II and III studies.SettingOperating room.Patients1855 adults undergoing surgery under general anesthesia and receiving rocuronium or vecuronium for NMB.InterventionsSugammadex (2.0 mg/kg at second twitch reappearance [T₂; moderate NMB], 4.0 mg/kg at 1–2 post-tetanic counts [PTC; deep NMB] or 16.0 mg/kg at 3 min after rocuronium 1.2 mg/kg), neostigmine or placebo.MeasurementsTime to recovery of the train-of-four (TOF) ratio to 0.9.Main resultsGeometric mean (95% CI) times to recovery to TOF ratio of 0.9 were 1.9 (1.8–2.0) min following sugammadex 2.0 mg/kg and 10.6 (9.8–11.6) min following neostigmine administration at T₂ after rocuronium, and 2.9 (2.5–3.4) min and 17.4 (13.4–22.6) min, respectively, after vecuronium. Recovery times were 2.2 (2.1–2.3) min following sugammadex 4.0 mg/kg and 19.0 (14.8–24.6) min following neostigmine administered at a target of 1–2 PTC after rocuronium, and 3.8 (3.0–5.0) min and 67.6 (56.3–81.2) min after vecuronium. Sugammadex administered 3 min after rocuronium 1.2 mg/kg resulted in rapid recovery (1.7 [1.5–2.0] min). Modest increases in mean recovery time were associated with vecuronium use (+ 1.6 min [78%; (61%–98%)] versus rocuronium), mild-to-moderate renal impairment (+ 0.4 min [20%; (9%–32%)] versus normal renal function) and geographic location (+ 1.0 min [38%; (25%–52%)] in subjects in USA/Canada versus Europe/Japan).ConclusionsSugammadex administered at recommended doses provides rapid and predictable reversal of rocuronium and vecuronium-induced moderate and deep NMB, and effective reversal 3 min after rocuronium 1.2 mg/kg. Robust recovery was seen across various patient factors, providing further confirmation of labeled dose recommendations.     

Retrospective Investigation of Grafted Kidney Function After Reversal of Neuromuscular Blockade Using Neostigmine or Sugammadex

IntroductionSugammadex has the steroid-encapsulating effect that reverses neuromuscular block induced by aminosteroid neuromuscular-blocking agents. Sugammadex can interact with other drugs that have the same steroidal structure with rocuronium, such as corticosteroids. Corticosteroids play a crucial role in the immunosuppression of kidney transplantation. The purpose of this study was to determine if there are any differences in grafted kidney function in recipients of kidney transplantation when sugammadex or neostigmine is given to the recipient.MethodsThe study included 42 recipients of kidney transplant, with complete, readable medical charts and anesthetic records. Fourteen recipients’ neuromuscular block was reversed with sugammadex (group S) and 28 recipients’ neuromuscular block was reversed with neostigmine (group N). We tested noninferiority for serum creatinine during the preoperative period and 5 days after transplantation. Short-term (28 days) outcomes of kidney transplantations were assessed by the incidence of acute rejection episodes, graft failure, length of stay at hospital, and mortality.ResultsThere were no significant differences in demographic characteristics, serum creatinine values, short-term outcomes, and graft survival rates at 28 days’ postoperatively between group S and group N (P > .05).ConclusionsOur data showed no difference in risk of serious adverse effects on short-term graft functions in patients who underwent kidney transplantation. However, considering the sugammadex-corticosteroids interaction, the immunosuppression and long-term effects on grafted kidney functions, current safety experience is insufficient to support the recommendation of routine sugammadex use in this population. These results need to be confirmed by sufficiently powered, controlled, pharmacokinetic, and pharmacodynamic studies on larger patient populations.     

Therapeutic efficacy of extracellular vesicles to suppress allograft rejection in preclinical kidney transplantation models: A systematic review and meta-analysis

BackgroundKidney transplantation is the optimal treatment of end-stage renal disease. Extracellular vesicles (EVs) have tremendous therapeutic potential, but their role in modulating immune responses in kidney transplantation remains unclear.MethodsWe performed a systematic review and meta-analysis to investigate the therapeutic efficacy of EVs in preclinical kidney transplant models. Outcomes for meta-analysis were graft survival and renal function. Subgroup analysis was conducted between immune cell derived EVs (immune cell-EVs) and mesenchymal stromal cell derived EVs (MSC-EVs).ResultsSeven studies published from 2013 to 2021 were included. The overall effects showed that EVs had a positive role in prolonging allograft survival (standardized mean difference (SMD) = 2.00; 95% confidence interval (CI), 0.79 to 3.21; P < 0.01; I² = 94%), reducing serum creatinine (SCr) (SMD = -2.19; 95%CI, ?3.35 to ?1.04; P < 0.01; I² = 93%) and blood urea nitrogen (BUN) concentrations (SMD = -1.69; 95%CI, ?2.98 to ?0.40; P = 0.01; I² = 94%). Subgroup analyses indicated that only immune cell-EVs significantly prolonged graft survival and improve renal function but not MSC-EVs.ConclusionsEVs are promising candidates to suppress allograft rejection and improve kidney transplant outcome. Immune cell-EVs showed their superiority over MSC-EVs in prolonging graft survival and improving renal function. For interpretation of the outcomes, additional studies are needed to validate these findings.     

Is There a Correlation with Pre-donation Kidney Volume and Renal Function in the Renal Transplant Recipient?: A Volumetric Computed Tomography Study

PurposeThe aim of this study is to determine the correlation between the predonation computed tomography (CT)-based calculated kidney volume and post-transplant renal function in recipients of renal transplants and to compare two different CT techniques.Material and methodsThe study group is comprised of 55 paired living kidney donor-recipients transplants. The total parenchymal renal volumes were calculated by using two CT-based techniques (3-dimensional renal volume [3DRV] and voxel-based volume calculation). Post-transplant creatinine and estimated glomerular filtration rate (eGFR) levels for the recipients at hospital discharge and sixth month were obtained. We tested the association with eGFR and creatinine by adjusting the renal volume to body weight and body mass index. For the creatinine levels above 1.5 mg/dL at discharge, a threshold value for renal volume-to-weight ratio on receiver operating characteristic curve (ROC) analysis and odds ratio (OR) were calculated.ResultsThe renal volumes adjusted to weight were found to be moderately correlated with eGFR and creatinine levels at discharge (r = 0.51 and r = −0.54 for voxel-based calculation; r = 0.52 and r = −0.52 for 3DRV calculation, P < .001, respectively) and at sixth month (r = 0.55 and r = −0.58 for voxel-based calculation; r = 0.51 and r = −0.54 for 3DRV calculation, P < .001 respectively). A threshold value of 1.84 mL/kg was calculated for parenchymal volume-to-recipient weight ratio on ROC analysis (AUC±SE, 0.760 ± 0.078, P = .008). The likelihood of creatinine elevation above 1.5 mg/dL was found to be nine times greater for smaller renal volume-to-recipient weight ratios (OR = 9.6; 95% CI, 1.8–50.6)ConclusionsPredonation renal volume adjusted to recipient weight may estimate the renal function at discharge and 6 months after transplantation.     

Sugammadex versus neostigmina em pacientes pediátricos: estudo prospectivo e randomizado

Background and objectivesAcetylcholinesterase inhibitors may cause postoperative residual curarization when they are used for reversal of neuromuscular blockade. Sugammadex reverses neuromuscular blockade by chemical encapsulation and is not associated with the side effects that may occur with the use of anticholinesterase agents. Because of increased outpatient surgical procedures postoperative residual curarization and rapid postoperative recovery have a greater importance in the pediatric patient population. The aim of this study was to compare the efficacy of sugammadex and neostigmine on reversing neuromuscular blockade in pediatric patients undergoing outpatient surgical procedures.Methods80 patients, aged 2–12 years, scheduled for outpatient surgery were enrolled in this randomized prospective study. Neuromuscular blockade was achieved with 0.6 mg kg⁻¹ rocuronium and monitorized with train‐of‐four. Group RN (n = 40) received 0.03 mg kg⁻¹ neostigmine, Group RS (n = 40) received 2 mg kg⁻¹ sugammadex for reversal of rocuronium. Extubation time (time from the reversal of neuromuscular blockade to extubation), train‐of‐four ratio during this time, time to reach train‐of‐four > 0.9, and probable complications were recorded.ResultsThere was no significant difference between the patients’ characteristics. Extubation time and time to reach train‐of‐four > 0.9 were significantly higher in Group RN (p = 0.001, p = 0.002). Train‐of‐four at the time of neostigmine/sugammadex injection in Group RN were significantly higher than in the RS group (p = 0.020). Extubation train‐of‐four ratio was significantly lower in Group RN (p = 0.002).ConclusionSugammadex provides safer extubation with a shorter recovery time than neostigmine in pediatric patients undergoing outpatient surgical procedures.     

Retrospective analysis of 30-day unplanned readmission after major abdominal surgery with reversal by sugammadex or neostigmine

Background

Sugammadex is associated with fewer postoperative complications, but its impact on 30-day unplanned readmission is unclear.

Sugammadex versus neostigmine for reversal of rocuronium-induced neuromuscular blockade: A randomized,double-blinded study of thoracic surgical patients evaluating hypoxic episodes in the early postoperative period

Study objectiveThis objective of this study was to determine if reversal of rocuronium-induced neuromuscular blockade with sugammadex versus neostigmine results in a decreased number of hypoxic episodes in the early postoperative period in patients undergoing thoracic surgery with single lung ventilation.DesignSingle-center, randomized, double-blind, two-arm clinical trial.SettingOperating room and postanesthesia care unit.Patients92 subjects aged ≥18, American Society of Anesthesiologists physical status II-IV, and undergoing a thoracic operation necessitating single lung ventilation.InterventionsSubjects received either 2 mg/kg sugammadex or 50 μg/kg neostigmine with 8 μg/kg glycopyrrolate for reversal of moderate neuromuscular blockade.MeasurementsFor the first 90 min postoperatively, all episodes of hypoxia were recorded. Neuromuscular monitoring was performed with acceleromyography (TOF-Watch® SX) and the train of four (TOF) was recorded at 2, 5, 10, and 15 min after administration of the neuromuscular reversal agent.Main resultsSubjects who received neostigmine had a median of 1 episode (interquartile range IQR: 0–2.2) of hypoxia versus subjects who received sugammadex who had a median of 0 episodes (IQR: 0–1) (p = 0.009). The mean time to recovery of TOF ≥ 0.9 was significantly faster with sugammadex at 10 min (95% confidence interval CI: 5–15) compared with neostigmine at 40 min (95% CI: 15–53) (p < 0.001).ConclusionsIn thoracic surgical patients necessitating single lung ventilation, sugammadex provides faster reversal of moderate neuromuscular blockade and results in a decreased number of postoperative hypoxic episodes compared with neostigmine.     

Effect of Mannitol on Kidney Function After Kidney Transplantation: A Systematic Review and Meta-Analysis

BackgroundThe effect of mannitol usage during kidney donation and kidney transplantation is still unclear. Therefore, we performed a systematic review and meta-analysis to research the difference in graft function between kidney grafts treated with and without mannitol.MethodsA literature search was performed in 5 databases and included 8 eligible studies out of 3570 references, which were included up to July 12, 2021. Relevant outcomes for analysis were graft survival, rejection, acute renal failure, delayed graft function, renal failure, creatinine clearance, diuresis, and serum creatinine.ResultsEight studies were identified, 1 study examining the effect of mannitol during kidney donation and 7 studies during kidney transplantation, of which 6 eligible for meta-analysis. A total of 1143 patients were included in these studies. The following outcome measures demonstrated significant differences in favor of mannitol usage compared with a control group: acute renal failure (risk ratio [RR], 0.45; 95% confidence interval [CI], 0.26–0.79; P < .01]) and delayed graft function (RR, 0.25; 95% CI, 0.08–0.77; P = 0.02 and RR, 0.69; 95% CI, 0.51–0.94; P = 0.94). Differences in other outcome parameters were not significant.ConclusionsThis systematic review and meta-analysis suggested that the use of mannitol during kidney transplantation leads to lower incidence of acute renal failure and delayed graft function. For all other outcomes, no significant difference was found. Further research should be conducted on the use of mannitol during donor nephrectomy because of the limited availability of studies. Finally, for interpretation of the outcomes, the quality of the evidence should be taken into consideration and we emphasize the need for more up-to-date research.     

Effect of Manganese on the Efficacy of Preservative Solution in Protecting Isolated Porcine Kidneys

BackgroundManganese is a bioelement essential for the proper functioning of the body. Mn²⁺ is a cofactor for many enzymes, including manganese superoxide dismutase. Together with the enzymes, it participates in cell defense against reactive oxygen species, immune response, and energy production in mitochondria. The aim of this study was to evaluate the effect of manganese added to Biolasol solution on the storage efficiency of isolated pig kidneys.MethodsTwenty kidneys from Polish Great White pigs were used in the study. Biolasol solution was modified with the addition of Mn²⁺ at a concentration of 1 µg/L. Grafts were assigned to 2 groups: A/Biolasol (n = 10) and B/Biolasol + Mn²⁺ (n = 10). The kidneys were washed with the developed solutions, then stored using the static method for 48h under hypothermia (4°C) and washed again. Markers of normal renal function were analyzed in the collected perfusates—aspartate aminotransferase (AST), alanine aminotransferase (ALT), protein, creatinine, urea, and electrolytes.ResultsAfter 48 hours and 30 minutes of renal preservation, activities/concentrations of biochemical parameters in the Biolasol + Mn²⁺ group increased (ALT: by 33%; AST: by 86%; urea: by 18%; creatinine: 3.25-fold [P < .05]) vs Biolasol. K⁺ ion concentration was 33% lower in the Biolasol group after 48 hours and 30 minutes (P < .05) vs group B. The presence of manganese in the composition of Biolasol solution influenced the maintenance of optimal Na⁺ ion concentration.ConclusionsManganese added to the Biolasol solution formulation at a dose of 1 µg/L showed low efficacy in protecting nephrons. We do not recommend adding manganese to the preservative solution formulation.     

Noninvasive Perioperative Monitoring of Arterial Function in Patients With Kidney Transplantation

Development of atherosclerosis is accelerated in kidney transplant recipients. Impaired metabolic pathways have a complex effect on the arterial wall, which can be measured by noninvasive techniques. Few data are available on the change of stiffness parameters in the postoperative course, so in this study we analyzed the stiffness parameters of kidney transplant recipients during the perioperative period. Seventeen successful primary kidney transplant patients with uneventful postoperative period (7 woman, 10 men; 46.16 ± 12.19 years) were involved in our short-term prospective longitudinal study. We analyzed the correlation between noninvasively assessed stiffness parameters (pulse wave velocity [PWV], augmentation index [AIx], pulse pressure [PP], systolic area index, diastolic area index, diastolic reflection area), ankle-brachial index (ABI), and laboratory parameters (creatinine, glomerular filtration rate, urea, haemoglobin, C-reactive protein). Stiffness parameters were measured with a Tensiomed Arteriograph. These parameters were assessed before the transplantation, and 24 hours, and 1 and 2 weeks after surgery under standard conditions. We found that creatinine (P = .0008) and C-reactive protein (P = .006) serum levels decreased, and glomerular filtration rate increased significantly (P = .0005). We revealed that PWV (P = .0075) and AIx (P = .013) improved significantly. There was no significant change in ABI, PP, and the other monitored parameters. Along with the available data in the literature, our findings suggest that kidney transplantation has a positive effect on the arterial function.     

Incidence of residual neuromuscular blockade and use of neuromuscular blocking agents with or without antagonists: A systematic review and meta-analysis of randomized controlled trials

ObjectivesNeuromuscular blocking agents (NMBAs) have revolutionized the field of anesthesiology as they facilitate airway management and ensure optimal surgical conditions. Despite their beneficial and ubiquitous use during surgery, delayed or partial recovery from NMBAs, referred to as residual neuromuscular block (rNMB), is a common clinical problem. While it is well accepted that the antagonist sugammadex, compared to neostigmine, can more rapidly reverse rocuronium-induced NMB regardless of depth of block, the occurrence of rNMB for routinely used combinations of NMBAs with sugammadex or neostigmine has not yet been quantified or evaluated systematically.Review methodsWe conducted a systematic literature review and meta-analysis of randomized controlled trials (RCTs) to quantify and compare the incidence of rNMB [defined as train-of-four ratio (TOFR) <0.9] in patients with moderate and deep neuromuscular block. Methods recommended by Cochrane Collaboration and PRISMA group were followed.ResultsA total of 35 RCTs were identified, of which 20 contributed to the meta-analysis. For moderate block, rNMB incidence at 2 min after sugammadex administration was 19.2% (95% CI 0.0–57.8; 122 patients) and declined to 2.8% (95% CI 0.0–16.7; 93 patients) at 6 min post administration. For timepoints 10 to 60 min after administration, rNMB incidence ranged between 0.05% to 2.8%. In contrast, rNMB incidence at 2 min after neostigmine administration was 100% (95% CI 89.9–100; 182 patients) and was 82% (95% CI 71.4–91.2; 93 patients) at 6 min post administration. For timepoints 10 to 60 min after administration, rNMB incidence ranged between 14 and 32%. For deep block, rNMB incidence following sugammadex was essentially reduced to 1% at 15 min after administration. Residual NMB incidence following neostigmine remained at or above 95% for the first 60 min after administration.ConclusionsOverall, based on evidence from 20 RCTs, our results suggest that the combination of rocuronium or vecuronium plus sugammadex is more effective and more rapid in reversing NMB compared with combinations of rocuronium, vecuronium, cisatracurium, or pancuronium plus neostigmine.     

Patient and Graft Survival After Dual Kidney Transplantation With Marginal Donors in Comparison to Matched Control Groups

BackgroundPostmortal organ donor rates remain low in Germany, whereas donor age has been increasing considerably in the last decades. As a consequence of low donation rates older and more marginal donor kidneys are accepted for transplantation. However, procured kidneys from very old a/o marginal donors may be considered as not suitable for transplantation as a single organ and subsequently be discarded. However, dual transplantation of both kidneys from such donors may provide an opportunity to nevertheless use these organs for renal transplantation, thereby providing the twofold nephron mass as a single kidney transplantation.MethodsWe compared in this retrospective analysis the outcome of 10 recipients of a dual kidney transplantation (DKT) with 40 matched recipients of a single kidney transplantation (SKT). Recipients were matched for donor and recipient age (ie, a maximum age difference of ±10 years in a ratio of 1:4 for DKT vs SKT recipients). In addition, a second SKT control group of 10 SKT recipients being transplanted immediately before each DKT recipient with a kidney from a donor aged ≥65 years was used for comparison. All renal transplant recipients were observed for up to 3 years or until July 31, 2020.ResultsMean donor and recipient age was 77.2 ± 4.6/75.1 ± 6.6/82.1 ± 7.9 and 66.4 ± 5.8/66.1 ± 6.0/64.8 ± 8.4 for SKT group 1/SKT group 2/DKT, respectively. Procurement serum creatinine concentrations were significantly higher in the DKT group in comparison to the SKT control group 1 (P = .019) as was the rate of transplant artery atherosclerosis (P = .021). Furthermore, Kidney Donor Profile Index, and Kidney Donor Risk Index were significantly higher (P = .0138/P = .064, and P < .001/P = .038) in the DKT group than in SKT group 1 and 2. Rates of acute rejection and delayed graft function were not significantly different between groups, though biopsy-proven acute rejection was numerically higher in the SKT groups. Patient survival and overall and death-censored graft survival rates were also not significantly different between groups, although they tended to be higher after DKT.ConclusionsDKT provides an opportunity to successfully use postmortal kidneys even from donors aged >80 years and a Kidney Donor Profile Index ≥95% for renal transplantation. DKT may thereby increase the available pool of donors to better serve patients with end-stage renal disease on the waiting list.     

Dopamine Treatment of Brain-Dead Fisher Rats Improves Renal Histology But Not Early Renal Function in Lewis Recipients After Prolonged Static Cold Storage

BackgroundBrain death (BD) and cold preservation are major risk factors for an unfavorable transplantation outcome. Although donor dopamine treatment in brain-dead rats improves renal function and histology in allogeneic recipients, it remains to be assessed if this also holds true for the combinations of BD and prolonged static cold preservation.MethodsBD was induced in F344 donor rats, which were subsequently treated with NaCl 1 mL/h (BD, n = 11), NaCl/hydroxy ethyl starch (BD-norm, n = 10), or 10 μg/min/kg dopamine (BD-dopa, n = 10). Renal grafts were harvested 4 h after BD and transplanted into bilateral nephrectomized Lewis recipients 6 h after cold preservation in University of Wisconsin solution. Renal function was evaluated by use of serum creatinine and urea concentrations at days 0, 1, 3, 5, and 10. Ten days after transplantation, recipients were killed and the renal allografts were processed for light microscopy and immune histology.ResultsSerum urea concentrations at days 5 and 10 were significantly lower in recipients that received a renal graft from dopamine-treated rats; for serum creatinine, only a trend was observed at day 10. Immune histology revealed a lower degree of ED1-positive cells in the donor dopamine-treated group. Under light microscopy, Banff classification revealed significantly less intimal arteritis in these grafts (P < .05).ConclusionsAlthough donor dopamine treatment clearly improves renal histology in this model, the beneficial effect on early renal function was marginal. It remains to be assessed if donor dopamine treatment has a beneficial effect on renal function in long-term follow-up.     

Role of Systemic Inflammatory Markers in Pediatric Kidney Transplantation

BackgroundNeutrophil-lymphocyte ratio (NLR), platelet-lymphocyte ratio (PLR), systemic immune-inflammation index (SII = N × P/L), and neutrophil percentage-albumin ratio (NPAR) have become accepted markers of inflammation in recent years. These indices are used as indicators of disease activity, mortality, and morbidity in many diseases. This study evaluated the relationship between inflammatory indices and graft function in pediatric kidney transplant recipients.MethodsMedical records of pediatric patients who underwent kidney transplantation at Ege University between 1995 and 2020 were reviewed retrospectively. Demographic, clinical, and laboratory data were recorded during the third month, first year, and fifth year of transplantation and at the last visit.ResultsThe median age of the 119 patients (60 boys/59 girls) at the time of transplantation was 154 months, and the median follow-up period was 101 months. According to Spearman correlation analysis, patients' final creatinine levels were positively correlated with NLR (r = 0.319), PLR (r = 0.219), SII (r = 0.214), and NPAR (r = 0.347) of the last visit; final estimate glomerular filtration rate levels were negatively correlated with NLR (P = .010, r = −0.250) and NPAR (P = .004, r = −0.277). The median NPAR of the patients with chronic allograft dysfunction at the last visit was found to be statistically significantly higher than without (P = .032).ConclusionNLR, PLR, SII, and NPAR values are correlated with creatinine levels after 5 years of kidney transplantation. The NPAR and final creatinine levels had the highest correlation coefficient among these inflammatory markers. These results suggest that inflammatory markers, especially NPAR, may be a candidate to be an indicator of ongoing inflammation in the graft.     

Acute Kidney Injury After Pediatric Liver Transplantation

BackgroundThe aim of the present study is to assess acute kidney injury (AKI) incidence according to the pRIFLE and AKIN criteria and to evaluate the risk factors for early developing AKI in postoperative intensive care unit after pediatric liver transplantation (LT).MaterialsAfter exclusion of retransplantations, 7 cadaveric and 44 living donors, totaling 51 pediatric LT patients that were performed between 2005 and 2017, were reviewed retrospectively. AKI was defined according to both pediatric RIFLE (Risk for renal dysfunction, Injury to the kidney, Failure of kidney function, Loss of kidney function, and End-stage renal disease) and Acute Kidney Injury Network (AKIN) criteria. Documented data were compared between AKI and non-AKI patients.ResultsAKI incidences were 17.6% by AKIN and 37.8% by pRIFLE criteria. AKIN-defined AKI group had statistically lower serum albumin level, higher serum sodium level, higher furosemide dose, and higher rate of red blood cell (RBC) transfusion than the non-AKI group (P = .02, P = .02, P = .01 and P = .04, respectively). AKI patients had significantly prolonged mechanical ventilation (P = .01) and hospital LOS (P = .02). The pRIFLE-defined AKI group had significantly lower serum albumin level, higher blood urea nitrogen (BUN) level, and higher ascites drained and also showed higher requirement for RBC and 20% human albumin transfusions than the non-AKI group (P = .02, P = .04, P: =.007, P = .02 and P = .05, respectively).ConclusionWe evaluated that hypoalbuminemia, high requirement for RBC and 20% human albumin transfusions, high serum sodium, high furosemide use, and high flow of ascites are risk factors for AKI and high BUN levels can be predictive for AKI in pediatric LT patients. The effect of AKI on outcome variables were prolonged mechanical ventilation and hospital LOS.