Reversal of residual neuromuscular block with neostigmine or sugammadex and postoperative pulmonary complications: a prospective, randomised, double-blind trial in high-risk older patients.

BACKGROUND: Residual neuromuscular block is associated with an increased risk of postoperative pulmonary complications in retrospective studies. The aim of our study was to investigate prospectively the incidence of postoperative pulmonary complications after reversal with either sugammadex (SUG) or neostigmine (NEO) in high-risk older patients. METHODS: We randomly allocated 180 older patients with significant morbidity (ASA physical status 3) ≥75 yr old to reversal of rocuronium with either SUG or NEO. Adverse events in the recovery room and pulmonary complications (defined by a 5-point [0-4; 0=best to 4=worst] outcome score) on postoperative Days 1, 3, and 7 were compared between groups. RESULTS: Data from 168 patients aged 80 (4) yr were analysed; SUG vs NEO resulted in a reduced probability (0.052 vs 0.122) of increased pulmonary outcome score (impaired outcome) on postoperative Day 7, but not on Days 1 and 3. More patients in the NEO group were diagnosed with radiographically confirmed pneumonia (9.6% vs 2.4%; P=0.046). The NEO group showed a non-significant trend towards longer hospital length of stay across all individual centres (combined 9 vs 7.5 days), with a significant difference in Malaysia (6 vs 4 days; P=0.011). CONCLUSIONS: Reversal of rocuronium neuromuscular block with SUG resulted in a small, but possibly clinically relevant improvement in pulmonary outcome in a select cohort of high-risk older patients. CLINICAL TRIAL REGISTRATION: ACTRN12614000108617.

International survey of neuromuscular monitoring in two European countries: a questionnaire study among Hungarian and Romanian anaesthesiologists.

BACKGROUND: Accumulating evidence indicates that objective neuromuscular monitoring and pharmacological reversal of neuromuscular block reduces the occurrence of residual muscle paralysis in the acute postoperative phase. However, objective neuromuscular monitoring is not a routine habit in anaesthesia. In order to change this situation, we wished to find out, as a first step to improvement, the current use of neuromuscular monitors and the custom of anaesthetists for reversal of neuromuscular block before tracheal extubation. METHODS: A ten-point questionnaire was available via the Surveymonkey website and the link was sent to 2202 Hungarian and Romanian anaesthetists by email. RESULTS: Three hundred and two (13.7%) of the 2202 registered anaesthetists responded. Less than 10% of them regularly use neuromuscular monitors. They underestimated the occurrence of residual block; only 2.2% gave a correct answer. Neuromuscular monitors are available in 74% of hospitals but are scarcely used. One third of anaesthetists rarely or never use reversal; approximately 20% regularly reverse before extubation. The responders typically believe that clinical signs of residual block are reliable. Instead of monitoring, they use the "timing methods" for tracheal extubation such as time elapsed from last dose, the duration of action of relaxant, the number of top-up doses, the cumulative dose, the return of adequate respiratory tidal volume and the ability to sustain a 5 s head lift. CONCLUSIONS: We concluded that neuromuscular monitoring in these two European countries is suboptimal as is the reversal strategy. Given the fact that monitors are available in the hospitals, the mentality should be changed towards evidence based practice.

Reversal of Deep Pipecuronium-Induced Neuromuscular Block With Moderate Versus Standard Dose of Sugammadex: A Randomized, Double-Blind, Noninferiority Trial.

BACKGROUND: Certain surgical interventions may require a deep neuromuscular block (NMB). Reversal of such a block before tracheal extubation is challenging. Because anticholinesterases are ineffective in deep block, sugammadex 4 mg/kg has been recommended for the reversal of rocuronium- or vecuronium-induced deep NMB. However, this recommendation requires opening 2 vials of 200 mg sugammadex, which results in an increase in drug costs. Therefore, we sought a less expensive solution for the induction and reversal of deep NMB. Although the optimal dose of sugammadex for antagonism of deep block from pipecuronium has not been established, data pertaining to moderate block are available. Accordingly, we hypothesized that sugammadex 2 mg/kg would be a proper dose to reverse deep pipecuronium block, enabling us to avoid cost increases. In the present study, we compared sugammadex 2 mg/kg with the standard dose of 4 mg/kg for reversal of deep block from pipecuronium. METHODS: This single-center, randomized, double-blind, 2 parallel-arms, noninferiority study comprised 50 patients undergoing general anesthesia with propofol, sevoflurane, fentanyl, and pipecuronium. Neuromuscular monitoring was performed with acceleromyography (TOF-Watch SX). Noninferiority margin was specified beforehand as an increase in reversal time of no >10% (corresponding to 1 minute for the primary outcome). When the block spontaneously recovered to posttetanic count 1, the patients randomly received sugammadex 2 or 4 mg/kg, and the time from the injection to the train-of-four (TOF) ratio of 1.0 was measured. Primary outcome was the time to achieve the normalized TOF ratio of 0.9 in a particular patient. Residual or recurrent postoperative NMB was additional end point. RESULTS: Each patient recovered to the normalized TOF ratio of 0.9. In the 2 mg/kg group, reversal time was 1.73 ± 1.03 minutes (95% confidence interval [CI], 1.33-2.13; n = 25), and in the 4 mg/kg group, reversal time was 1.42 ± 0.63 minutes (mean ± standard deviation) (95% CI, 1.17-1.67; n = 25). The mean difference in reversal times between the 2 groups was 0.31 minutes (95% CI, -0.18 to 0.8), and the upper limit of CI was below the noninferiority margin of 1 minute. Postoperative block did not occur. CONCLUSIONS: The effect of sugammadex 2 mg/kg was noninferior to that of 4 mg/kg in reversing posttetanic count-1 degree pipecuronium block. Sugammadex reversal of deep pipecuronium block appears to be effective.

Reversal of Vecuronium-induced Neuromuscular Blockade with Low-dose Sugammadex at Train-of-four Count of Four: A Randomized Controlled Trial.

BACKGROUND: Rocuronium-induced neuromuscular block that spontaneously recovered to a train-of-four count of four can be reversed with sugammadex 0.5 or 1.0 mg/kg. We investigated whether these doses of sugammadex can also reverse vecuronium at a similar level of block. METHODS: Sixty-five patients were randomly assigned, and 64 were analyzed in this controlled, superiority study. Participants received general anesthesia with propofol, sevoflurane, fentanyl, and vecuronium. Measurement of neuromuscular function was performed with acceleromyography (TOF-Watch-SX, Organon Teknika B.V., The Netherlands ). Once the block recovered spontaneously to four twitches in response to train-of-four stimulation, patients were randomly assigned to receive sugammadex 0.5, 1.0, or 2.0 mg/kg; neostigmine 0.05 mg/kg; or placebo. Time from study drug injection to normalized train-of-four ratio 0.9 and the incidence of incomplete reversal within 30 min were the primary outcome variables. Secondary outcome was the incidence of reparalysis (normalized train-of-four ratio less than 0.9). RESULTS: Sugammadex, in doses of 1.0 and 2.0 mg/kg, reversed a threshold train-of-four count of four to normalized train-of-four ratio of 0.9 or higher in all patients in 4.4 ± 2.3 min (mean ± SD) and 2.6 ± 1.6 min, respectively. Sugammadex 0.5 mg/kg reversed the block in 6.8 ± 4.1 min in 70% of patients (P < 0.0001 vs. 1.0 and 2.0 mg/kg), whereas neostigmine produced reversal in 11.3 ± 9.7 min in 77% of patients (P > 0.05 vs. sugammadex 0.5 mg/kg). The overall frequency of reparalysis was 18.7%, but this incidence varied from group to group. CONCLUSIONS: Sugammadex 1.0 mg/kg, unlike 0.5 mg/kg, properly reversed a threshold train-of-four count of four vecuronium-induced block but did not prevent reparalysis.

Impact of reversal strategies on the incidence of postoperative residual paralysis after rocuronium relaxation without neuromuscular monitoring: A partially randomised placebo controlled trial.

BACKGROUND: Electronic neuromuscular monitoring is not widely used to determine either the reversal requirements for neuromuscular block before extubation of the trachea, or to determine if there is any subsequent postoperative residual neuromuscular block (PORNB). OBJECTIVES: To investigate the incidence of PORNB using acceleromyography after spontaneous recovery of rocuronium-induced block and to compare this with the administration of sugammadex, neostigmine or a placebo. DESIGN: Partially randomised, partially randomised, placebo-controlled, double-blind, four-group parallel-arm study. SETTING: Single-centre study performed between October 2013 and December 2015 in a university hospital. PATIENTS: Of the 134 eligible patients, 128 gave their consent and 125 of these completed the study. INTERVENTIONS: Patients received general anaesthesia with propofol, sevoflurane, fentanyl and rocuronium. Neuromuscular transmission was measured by acceleromyography (TOF-Watch-SX; Organon Teknika B.V., Boxtel, the Netherlands) but the anaesthetist was blind to the results. If the anaesthetist deemed pharmacological reversal to be necessary before extubation of the trachea then patients were assigned randomly to receive either sugammadex (2.0 mg kg), neostigmine (0.05 mg kg) or a placebo. In the postanaesthesia care unit, an independent anaesthetist, unaware of the treatment given, assessed the neuromuscular function using acceleromyography. MAIN OUTCOME MEASURES: The incidence of a normalised train-of-four ratio less than 0.9 on arrival in the recovery room. RESULTS: In total, 125 patients were recruited. Neuromuscular block was allowed to recover spontaneously in 50 patients, whereas the remainder received either sugammadex (27), neostigmine (26) or placebo (22). The number of cases with PORNB were one (3.7%), four (15%), 13 (26%) and 10 (45%) after sugammadex, neostigmine, spontaneous recovery and placebo, respectively. Sugammadex and neostigmine were more effective than placebo [odds ratio (OR): 0.05, 95% confidence interval (CI): 0.005 to 0.403, P = 0.005; OR: 0.22, 95% CI: 0.056 to 0.85, P = 0.028, respectively]. Sugammadex performed better than spontaneous recovery (OR: 0.11, 95% CI: 0.014 to 0.89, P = 0.039) unlike neostigmine (OR: 0.52, 95% CI: 0.15 to 1.79, P = 0.297). Yet, antagonism (pooled data) was more effective than spontaneous recovery (OR: 0.3, 95% CI: 0.1 to 0.9, P = 0.03). CONCLUSION: Although pharmacological reversal based on clinical signs was superior to spontaneous recovery it did not prevent PORNB, irrespective of the reversal agent. TRIAL REGISTRATION: The study is registered under EUDRACT number 2013-001965-17.

[Favourable effects of kidney transplantation on vascular condition of patients: Potential prognostic significance of non-invasive measurement of arterial stiffness]. / A vesetranszplantáció pozitív hatásai a betegek angiológiai státuszára: Az artériás funkció (stiffness) noninvazív mérésének lehetséges szerepe az elorejelzésben.

INTRODUCTION: Development of atherosclerosis is accelerated in kidney transplant patients. Impaired metabolic pathways have complex effect on the arterial wall which can be measured by non-invasive techniques. Only few data are available on the change of stiffness parameters in the postoperative course. Therefore, in this study the authors analysed the stiffness parameters of kidney transplant recipients during the perioperative period. AIM: Non-invasive clinical trial of the arterial functional parameters in the early postoperative period. METHOD: Seventeen successful primary kidney transplant patients with uneventful postoperative period (8 females, 9 males; age, 46.16 ± 12.19 years) were involved in this short-term prospective longitudinal study. The authors analysed correlations between non-in vasively assessed stiffness parameters (pulse wave velocity PWV, augmentation index - AIx). Stiffness parameters were measured with a TensioMed Arteriograph. These parameters were assessed before the transplantation, as well as 24 hours, 1 and 2 weeks after surgery under standard conditions. RESULTS: It was found that PWV (p = 0.0075) and AIx (p = 0.013) improved significantly. There was no significant change in case of PP and the other monitored parameters. Serum creatinine decreased (p = 0.0008) and glomerular filtration rate increased significantly (p = 0.0005). CONCLUSIONS: Along with the available data in the literature, the findings suggest that kidney transplantation has a positive effect on the arterial function. Improvement can be detected non-invasively with Arteriograph in the early postoperative period.

[First outcomes, since being full member of Eurotransplant. A single center experience of cadaveric kidney transplantation]. / Eredményeink a teljes jogú Eurotransplant-tagság óta. A Debreceni Vesetranszplantációs Központ tapasztalatai.

INTRODUCTION: The first renal transplantation was completed in 1991 at the University of Debrecen. In 2013 Hungary joined Eurotransplant. AIM: The authors retrospectively compared the trends. METHOD: Comparison between Period A (from January 1, 2008 to August 31, 2013) and Period B (from September 1, 2013 to October 22, 2015). RESULTS: The proportion of living transplants rose from 3.5% to 9.1 %. During period B over 25% of utilized donors were over 60 years of age. Recipients with body mass index above 30 kg/m(2) increased from 12% to 31%. Prevalence of diabetes among recipients rose twofold. Uretero-neocystostomy was used during period A (99%) while in period B end to side uretero-ureteral anastomosis has also gained popularity (68%). In 2013 the authors introduced routine use of induction treatment. Acute rejection rate decreased from 34% to 8%. The rate of surgical complications did not change. Acute bacterial infections decreased from 41% to 33%. Cumulative renal allograft 1, 3 and 5 year survival rates were 86.6%, 85% and 82.7% in group A vs. projected rates 88%, 84% and 84% in group B, respectively. CONCLUSIONS: Despite the growing proportion of expanded criteria donors, the authors were able to maintain a low incidence of delayed graft function and a favorable graft survival. Since 2013 the authors introduced treatments for acute humoral rejection according to international standards.

[The effect of the I/D polymorphism of the angiotensin-converting enzyme gene on the cardiovascular risk and graft survival of kidney transplant patients]. / Az angiotenzinkonvertálóenzim-gén I/D polimorfizmusának hatása a vesetranszplantált betegek cardiovascularis rizikójára és a grafttúlélésre.

INTRODUCTION: Renal transplantation provides longer life expectancy in patients with renal failure. Nonetheless, this improved life expectancy is still shorter than that for the general population. The main couse of death in renal transplant patients is cardiovascular disease, and chronic allograft nephropathy is the most significant cause of graft loss. Genetic polymorphisms of the renin angiotensin system have been implicated in both chronic allograft nephropathy and fatal cardiovascular diseases. AIM: The long term goal of the authors was to improve the survival of renal transplanted patients. The authors aimed to identify novel biomarkers which correlate with the survival of the transplant organ and the recipient with a special attention to elements of the renin-angiotensin system. METHOD: A retrospective clinical trial was performed involving 72 renal transplanted patients. Angiotensin-converting enzyme I/D genotypes and activity, kidney function and morphological properties of the heart were determined. RESULTS: A significant positive correlation was found between the DD genotype of the angiotensin-converting enzíme gene, and the DD genotype predicted severe left ventricular hypertrophy. CONCLUSIONS: These findings suggest that the I/D genotypes of the angiotensin-converting enzyme gene predict not only the expected survival of the transplanted organ, but also that of the patient. Patients with the DD genotype are more susceptible for transplant failure. These patients should be identified and a special attention should be made on their pharmacological treatment (renin-angiotensin system inhibition), and their complience should also be maintained.

[Analysis of donor scoring systems in a single Hungarian transplant centre]. / Donorszelekciós kritériumok vizsgálata a debreceni veseátültetési programban.

INTRODUCTION: To ease organ shortage many transplant centres developed different donor scoring systems, however, a general consensus among clinicians on the use of these systems does not still exist. AIM: The aim of the authors was to analyse the effect of expanded criteria donor, deceased donor score and kidney donor risk index on postoperative kidney function and graft survival. METHOD: Analysis of the characteristics of 138 kidney transplantations and 205 donors in a retrospective study of a five-year period. RESULTS: There was a trend towards rejecting donors in higher risk groups; 22.7% of standard criteria donors belonged to the high risk group of deceased donor score. Graft function was worse in high risk patients. High risk donors can be divided due to the use of deceased donor score. Patients with the highest risk had worse graft function and survival. CONCLUSIONS: With the use of these scoring systems grafts with favourable outcome can be selected more precisely.

[Allograft nephrectomy - a single-center experience]. / Graftectomiák a debreceni vesetranszplantációs programban.

INTRODUCTION: Indication and timing of allograft nephrectomy is still uncertain in some cases. AIM: The aim of the authors was to summarize their experience with graftectomies. METHOD: Data from patients who underwent kidney transplantation between January 1, 2004 and December 31, 2015 were retrospectively analyzed. Frequency, indications, timing, complications as well as early and late allograft nephrectomies were reviewed. RESULTS: From 480 renal transplants, 55 graftectomies were performed (11%). Frequent indications included chronic allograft nephropathy (47%), arterial blood supply complications (13%), ureter complications (9%). 22 cases (40%) of allograft nephrectomies were urgent while 33 cases (60%) were elective. 24% of graftectomies were performed within 30 days after transplantation and 76% thereafter. CONCLUSIONS: The main indications for early graftectomies were arterial complications (31%) and chronic allograft nephropathy (62%) in cases of late graftectomies. The majority of the graftectomies were elective. Leading indication was chronic allograft nephropathy. Early and late graftectomies have different characteristics.

[Treatment options of non-melanoma skin tumors in organ transplant recipients in relation to a case report]. / Nonmelanoma bortumorok kezelési lehetoségei szervtranszplantált betegeknél egy esetismertetés kapcsán.

The authors present the case of a 59-year-old male patient, whose first kidney transplantation was in 1983 and the second in 2000. The first squamous cell carcinoma appeared on the skin 2 years after the first transplantation. Since 2003, at least two precancerous lesions or non-melanoma skin tumors have been removed surgically yearly. These cancers appeared predominantly on the sun-exposed skin, and were multiple. As these tumors could behave aggressively and prone to recurrence, complex treatment was applied, which included a switch in immunosuppressive drugs and the application of field therapies. The authors give an overview of these treatment options in relation to the case presentation, emphasizing that not only early detection and active treatment of the precancerous lesions and skin cancers are essential, but education of proper sun-protection methods and dermatology care are also important in order to avoid the development of these tumors.

Reversal of Pipecuronium-Induced Moderate Neuromuscular Block with Sugammadex in the Presence of a Sevoflurane Anesthetic: A Randomized Trial.

BACKGROUND: Pipecuronium is a steroidal neuromuscular blocking agent. Sugammadex, a relaxant binding γ-cyclodextrin derivative, reverses the effect of rocuronium, vecuronium, and pancuronium. We investigated whether sugammadex reverses moderate pipecuronium-induced neuromuscular blockade (NMB) and the doses required to achieve reversal. METHODS: This single-center, randomized, double-blind, 5-group parallel-arm study comprised 50 patients undergoing general anesthesia with propofol, sevoflurane, fentanyl, and pipecuronium. Neuromuscular monitoring was performed with acceleromyography (TOF-Watch SX) according to international standards. When the NMB recovered spontaneously to train-of-four count 2, patients randomly received 1.0, 2.0, 3.0, or 4.0 mg/kg of sugammadex or placebo. Recovery time from sugammadex injection to normalized train-of-four (TOF) ratio 0.9 was the primary outcome variable. The recovery time from the sugammadex injection to final T1 was the secondary end point. Postoperative neuromuscular functions were also assessed. RESULTS: Each patient who received sugammadex recovered to a normalized TOF ratio of 0.9 within 5.0 minutes (95% lower confidence interval for the lowest dose 70.1%; for all doses 90.8%) and 79% of these patients reached a normalized TOF ratio 0.9 within 2.0 minutes (95% lower confidence interval for the lowest dose 26.7%; for all doses 63.7%). T1 recovered several minutes after the TOF ratio. No residual postoperative NMB was observed. CONCLUSIONS: Sugammadex adequately and rapidly reverses pipecuronium-induced moderate NMB during sevoflurane anesthesia. Once the train-of-four count has spontaneously returned to 2 responses following pipecuronium administration, a dose of 2.0 mg/kg of sugammadex is sufficient to reverse the NMB.

WU and KI polyomaviruses in respiratory, blood and urine samples from renal transplant patients.

BACKGROUND: It is suggested that immunosuppression due to transplantation might be a risk for human polyomavirus KI (KIPyV) and WU (WUPyV) infection. Most of the publications report data about stem cell transplant patients, little is known about these virus infections in renal transplant patients. OBJECTIVES: To study the presence of KIPyV and WUPyV in upper respiratory, plasma and urine samples from renal transplant patients. To analyse clinical and personal data. STUDY DESIGN: 532 respiratory, 503 plasma and 464 urine samples were collected from 77 renal transplant patients. KIPyV and WUPyV were detected by nested and quantitative real-time PCR. Patient and clinical data from medical records were analyzed. RESULTS: KIPyV was detected in respiratory, plasma and urine samples from 14.3%, 3.9% and 4.1% of renal transplant patients. WUPyV was found in respiratory and plasma specimens from 9.1% and 5.3% of the patients. Significant association was revealed between the detection of KIPyV and WUPyV and the time of samples collection and the age of the patients. KIPyV was presented in respiratory and plasma sample at the same time. KIPyV was detected in plasma samples from two patients and in urine samples of three other patients providing also KIPyV positive respiratory samples at the same time. No clinical consequences of KIPyV or WUPyV infection were found. CONCLUSION: Although no clinical consequences of KIPyV and WUPyV infections were found in renal transplant patients, it is suggested that renal transplantation might result in higher susceptibility or reactivation of these infection.

Pregnancy management of women with kidney transplantation.

Women with renal disease, besides many dysfunctions, face increasing infertility and high-risk pregnancy due to uremia and changes of the hormonal functions. After renal transplantation, sexual dysfunction improves, providing the possibility of successful pregnancy for women of childbearing age. However, kidney transplanted patients are high-risk pregnant patients with increased maternal and fetal risks, and the graft also may be compromised during pregnancy; most studies report on several successive deliveries due to multidisciplinary team management. In clinical practice, the graft is rarely affected during the period of gestation. Fetal development disorders are also rare although preterm delivery and intrauterine growth retardation are common. For now, several studies and clinical investigations proved that, under multidisciplinary control, kidney transplanted female patients are also possible to have safe pregnancy and successful delivery. There are conflicting data in the literature about the prevention of complications and the timing of pregnancy. Herein, we would like to present some experience of our centre. A total of 847 kidney transplantations have been performed between June 1993 and December 2013 with 163 childbearing aged females (18-45 years) in our center. We report on three kidney transplanted patients who have given birth to healthy newborns. In our practice, severe complications have not been observed.

Prognosis of dialysed patients after kidney transplant failure.

BACKGROUND/AIMS: Patients with a failed kidney transplant represent a unique, high-risk chronic kidney disease population that is increasing in number, and may be sub-optimally managed. Our aim was to compare the survival of patients with failed allografts to patients with native kidney failure and to assess whether their survival is affected by the graft resection. METHODS: Kaplan-Meier and Cox-regression survival analyses were performed on the data of 57 patients with graft failure and of 123 transplant-naive haemodialysed patients. RESULTS: After adjustment for age and gender, there was no statistically significant difference in the mortality of patients in the two groups. The 43 patients, who had a transplanted kidney nephrectomy had a statistically not significant survival benefit over non-nephrectomised patients (age and gender adjusted hazard ratio: 0.56 95 % confidence interval: 0.24-1.58, p-value: 0.18). CONCLUSION: Elective graft resection is a safe, effective alternative for both the treatment and the prevention of the chronic inflammatory state associated with a failed kidney transplant.