Profile of sugammadex for reversal of neuromuscular blockade in the elderly: Current perspectives

The number of elderly patients is increasing worldwide. This will have a significant impact on the practice of anesthesia in future decades. Anesthesiologists must provide care for an increasing number of elderly patients, who have an elevated risk of perioperative morbidity and mortality. Complications related to postoperative residual neuromuscular blockade, such as muscle weakness, airway obstruction, hypoxemia, atelectasis, pneumonia, and acute respiratory failure, are more frequent in older than in younger patients. Therefore, neuromuscular blockade in the elderly should be carefully monitored and completely reversed before awakening patients at the end of anesthesia. Acetylcholinesterase inhibitors are traditionally used for reversal of neuromuscular blockade. Although the risk of residual neuromuscular blockade is reduced by reversal with neostigmine, it continues to complicate the postoperative course. Sugammadex represents an innovative approach to reversal of neuromuscular blockade induced by aminosteroid neuromuscular-blocking agents, particularly rocuronium, with useful applications in clinical practice. However, aging is associated with certain changes in the pharmacokinetics of sugammadex, and to date there has been no thorough evaluation of the use of sugammadex in elderly patients. The aim of this review was to perform an analysis of the use of sugammadex in older adults based on the current literature. Major issues surrounding the physiologic and pharmacologic effects of aging in elderly patients and how these may impact the routine use of sugammadex in elderly patients are discussed

Sugammadex for reversal of neuromuscular blockade: A retrospective analysis of clinical outcomes and cost-effectiveness in a single center

OBJECTIVE: The aim of the study is to evaluate the clinical and economic impact of introducing a rocuronium-neostigmine-sugammadex strategy into a cisatracurium-neostigmine regimen for neuromuscular block (NMB) management. METHODS: We conducted a retrospective analysis of clinical outcomes and cost-effectiveness in five operating rooms at University Hospital of Padova. A clinical outcome evaluation after sugammadex administration as first-choice reversal drug in selected patients (rocuronium-sugammadex) and as rescue therapy after neostigmine reversal (rocuronium-neostigmine-sugammadex) compared to control was performed. A cost-analysis of NMB management accompanying the introduction of a rocuronium-neostigmine-sugammadex strategy into a cisatracurium-neostigmine regimen was carried out. To such purpose, two periods were compared: 2011-2012, without sugammadex available; 2013-2014, with sugammadex available. A subsequent analysis was performed to evaluate if sugammadex replacing neostigmine as first choice reversal drug is cost-effective. RESULTS: The introduction of a rocuronium-neostigmine-sugammadex strategy into a cisatracurium-neostigmine regimen reduced the average cost of NMB management by 36%, from €20.8/case to €13.3/case. Patients receiving sugammadex as a first-choice reversal drug (3%) exhibited significantly better train-of-four ratios at extubation (P<0.001) and were discharged to the surgical ward (P<0.001) more rapidly than controls. The cost-saving of sugammadex as first-choice reversal drug has been estimated to be €2.9/case. Patients receiving sugammadex as rescue therapy after neostigmine reversal (3.2%) showed no difference in time to discharge to the surgical ward (P=0.44) compared to controls. No unplanned intensive care unit (ICU) admissions with rocuronium-neostigmine-sugammadex strategy were observed. The potential economic benefit in avoiding postoperative residual curarization (PORC)-related ICU admission in the 2013-2014 period was estimated at an average value of €13,548 (€9,316-€23,845). CONCLUSION: Sugammadex eliminated PORC and associated morbidities. In our center, sugammadex reduced the costs of NMB management and promoted rapid turnover of patients in operating rooms, with total cost-effectiveness that counteracts the disadvantages of its high cost

Isolated forearm technique: a meta-analysis of connected consciousness during different general anaesthesia regimens

BACKGROUND: General anaesthesia should prevent patients from experiencing surgery, defined as connected consciousness. The isolated forearm technique (IFT) is the current gold standard for connected consciousness monitoring. We evaluated the efficacy of different anaesthesia regimens in preventing IFT responses. METHODS: We conducted a systematic review with meta-analysis of studies evaluating IFT in adults. Proportions of IFT-positive patients were compared for inhalational versus intravenous anaesthesia and anaesthesia brain monitor (ABM)-guided versus non-ABM-guided. RESULTS: Of 1131 patients in 22 studies, 393 (34.8%) had an IFT response during induction or maintenance. IFT-positive patients were less frequent during induction (19.7% [95% CI, 17.5-22.1]) than during maintenance (31.2% [95% CI, 27.8-34.8]). Proportions of IFT-positive patients during induction and maintenance were similar for inhalational (0.51 [95% CI, 0.38-0.65]) and intravenous (0.52 [95% CI, 0.26-0.77]) anaesthesia, but during maintenance were lower with inhalational (0.18 [95% CI, 0.08-0.38]) than with intravenous (0.48 [95% CI, 0.24-0.73]) anaesthesia. Proportions of IFT-positive patients during induction and maintenance were not significantly different for ABM-guided (0.64 [95% CI, 0.39-0.83]) and non-ABM-guided (0.48 [95% CI, 0.34-0.62]) anaesthesia but during maintenance were lower with non-ABM-guided (0.19 [95% CI, 0.09-0.37]) than with ABM-guided (0.57 [95% CI, 0.34-0.77]). Proportions of IFT-positive patients decreased significantly with increasing age and premedication use. Of the 34 anaesthesia regimens, 16 were inadequate. Studies had low methodological quality (only seven randomised controlled trials) and significant heterogeneity. CONCLUSIONS: Standard general anaesthesia regimens might not prevent connected consciousness. More accurate anaesthesia brain monitor methodology to reduce the likelihood of connected consciousness is desirable

Dual effects of leptin in perioperative gas exchange of morbidly obese patients

Leptin has shown positive effects on respiratory function in experimental settings. The role of leptin on perioperative respiratory function in morbidly obese patients has not been established. We performed a retrospective analysis of morbidly obese patients undergoing laparoscopic sleeve gastrectomy. Fasting serum leptin and interleukin (IL)-6 were measured preoperatively, and arterial blood gases were obtained pre- and postoperatively. Outcome variables were arterial partial pressure of oxygen (PaO2), arterial partial pressure of carbon dioxide (PaCO2), and differences in PaO2 and PaCO2 between pre- and postoperative values (\u394PaO2, \u394PaCO2; postoperative minus preoperative). Patients with lower (<40 \u3bcg/L) and higher ( 6540 \u3bcg/L) leptin levels were compared. Bravais-Pearson's correlation, multiple linear regression, and logistic regression analysis were performed. A total of 112 morbidly obese patients were included. Serum leptin was significantly higher in females than in males (42.86\ub112.89 vs. 30.67\ub113.39 \u3bcg/L, p<0.0001). Leptin was positively correlated with body mass index (r = 0.238; p = 0.011), IL-6 (r = 0.473; p<0.0001), and \u394PaO2 (r = 0.312; p = 0.0008). Leptin was negatively correlated with preoperative PaO2 (r = -0.199; p = 0.035). Preoperative PaO2 was lower, \u394PaCO2 was smaller, and \u394PaO2 was greater in the high leptin group than in the low leptin group. In multiple regression analysis, leptin was negatively associated with preoperative PaO2 (estimate coefficient = -0.147; p = 0.023). In logistic regression analysis, leptin was associated with improved \u394PaO2 (odds ratio [OR] = 1.104; p = 0.0138) and \u394PaCO2 (OR = 0.968; p = 0.0334). Leptin appears to have dual effects related to perioperative gas exchange in obese patients undergoing bariatric surgery. It is associated with worse preoperative oxygenation but improved respiratory function after surgery

Pain-related Somato Sensory Evoked Potentials: A potential new tool to improve the prognostic prediction of coma after cardiac arrest

INTRODUCTION: Early prediction of a good outcome in comatose patients after cardiac arrest still remains an unsolved problem. The main aim of the present study was to examine the accuracy of middle-latency SSEP triggered by a painful electrical stimulation on median nerves to predict a favorable outcome. METHODS: No- and low-flow times, pupillary reflex, Glasgow motor score and biochemical data were evaluated at ICU admission. The following were considered within 72 h of cardiac arrest: highest creatinine value, hyperthermia occurrence, EEG, SSEP at low- (10 mA) and high-intensity (50 mA) stimulation, and blood pressure reactivity to 50 mA. Intensive care treatments were also considered. Data were compared to survival, consciousness recovery and 6-month CPC (Cerebral Performance Category). RESULTS: Pupillary reflex and EEG were statistically significant in predicting survival; the absence of blood pressure reactivity seems to predict brain death within 7 days of cardiac arrest. Middle- and short-latency SSEP were statistically significant in predicting consciousness recovery, and middle-latency SSEP was statistically significant in predicting 6-month CPC outcome. The prognostic capability of 50 mA middle-latency-SSEP was demonstrated to occur earlier than that of EEG reactivity. CONCLUSIONS: Neurophysiological evaluation constitutes the key to early information about the neurological prognostication of postanoxic coma. In particular, the presence of 50 mA middle-latency SSEP seems to be an early and reliable predictor of good neurological outcome, and its absence constitutes a marker of poor prognosis. Moreover, the absence 50 mA blood pressure reactivity seems to identify patients evolving towards the brain death

Prediction of difficult tracheal intubations in thyroid surgery. Predictive value of neck circumference to thyromental distance ratio

INTRODUCTION:Difficult tracheal intubation (DTI) contributes to perioperative morbidity and mortality. There are conflicting study results about the most predictive DTI risk criteria in patients undergoing thyroid surgery. MATERIALS AND METHODS:We conducted a prospective observational study on 500 consecutive patients aged 6518 years to identify predictors for DTI. Body weight, body mass index (BMI), inability to prognath, head movement, mouth opening, Mallampati score, neck circumference (NC), thyromental distance (TMD), neck circumference to thyromental distance ratio (NC/TMD), tracheal deviation apparent on chest x-ray, mediastinal goiter, histology and history of DTI were measured as possible predictors of DTI. Spearman's rank correlation test and multiple logistic regression analysis were performed. RESULTS:DTI was observed in 9.6% of all patients. Compared with the group of patients without DTI, the group of patients with DTI had significantly greater median values for body weight, BMI, NC, NC/TMD, Mallampati score, el-Ganzouri score, incidence of mediastinal goiter, and had reduced TMD and mouth opening. Significant correlations between BMI 6530 kg/m2 and the Mallampati score 653 (R = 0.124, p = 0.00541), Cormack-Lehane 653 (R = 0.128, p = 0.00409), NC 6540 cm (R = 0.376, p<0.001), and NC/TMD 655 (R = 0.103, p = 0.0207) were found. The logistic regression analysis revealed that an NC 6540 cm at the goiter level, but not an NC/TMD ratio 655, was the strongest predictor of DTI (p<0.001). The area under the receiver operating characteristic curve for NC/TMD was better than the curve for NC. The sensitivity and specificity of NC/TMD were also greater, compared with NC. An NC of 40.00 cm and an NC/TMD of 5.85 were the estimated cut-off points. DISCUSSION:This study found that NC was a strong predictor of DTI. The results also suggested that NC/TMD could be used as a measure to stratify the risk of DTI in patients undergoing thyroid surgery

The Atacama Cosmology Telescope: A Measurement of the DR6 CMB Lensing Power Spectrum and its Implications for Structure Growth

We present new measurements of cosmic microwave background (CMB) lensing over $9400$ sq. deg. of the sky. These lensing measurements are derived from the Atacama Cosmology Telescope (ACT) Data Release 6 (DR6) CMB dataset, which consists of five seasons of ACT CMB temperature and polarization observations. We determine the amplitude of the CMB lensing power spectrum at $2.3\%$ precision ($43\sigma$ significance) using a novel pipeline that minimizes sensitivity to foregrounds and to noise properties. To ensure our results are robust, we analyze an extensive set of null tests, consistency tests, and systematic error estimates and employ a blinded analysis framework. The baseline spectrum is well fit by a lensing amplitude of $A_{\mathrm{lens}}=1.013\pm0.023$ relative to the Planck 2018 CMB power spectra best-fit $\Lambda$CDM model and $A_{\mathrm{lens}}=1.005\pm0.023$ relative to the $\text{ACT DR4} + \text{WMAP}$ best-fit model. From our lensing power spectrum measurement, we derive constraints on the parameter combination $S^{\mathrm{CMBL}}_8 \equiv \sigma_8 \left({\Omega_m}/{0.3}\right)^{0.25}$ of $S^{\mathrm{CMBL}}_8= 0.818\pm0.022$ from ACT DR6 CMB lensing alone and $S^{\mathrm{CMBL}}_8= 0.813\pm0.018$ when combining ACT DR6 and Planck NPIPE CMB lensing power spectra. These results are in excellent agreement with $\Lambda$CDM model constraints from Planck or $\text{ACT DR4} + \text{WMAP}$ CMB power spectrum measurements. Our lensing measurements from redshifts $z\sim0.5$--$5$ are thus fully consistent with $\Lambda$CDM structure growth predictions based on CMB anisotropies probing primarily $z\sim1100$. We find no evidence for a suppression of the amplitude of cosmic structure at low redshiftsComment: 45+21 pages, 50 figures. Prepared for submission to ApJ. Also see companion papers Madhavacheril et al and MacCrann et a

Case Reports1. A Late Presentation of Loeys-Dietz Syndrome: Beware of TGFβ Receptor Mutations in Benign Joint Hypermobility

Background: Thoracic aortic aneurysms (TAA) and dissections are not uncommon causes of sudden death in young adults. Loeys-Dietz syndrome (LDS) is a rare, recently described, autosomal dominant, connective tissue disease characterized by aggressive arterial aneurysms, resulting from mutations in the transforming growth factor beta (TGFβ) receptor genes TGFBR1 and TGFBR2. Mean age at death is 26.1 years, most often due to aortic dissection. We report an unusually late presentation of LDS, diagnosed following elective surgery in a female with a long history of joint hypermobility. Methods: A 51-year-old Caucasian lady complained of chest pain and headache following a dural leak from spinal anaesthesia for an elective ankle arthroscopy. CT scan and echocardiography demonstrated a dilated aortic root and significant aortic regurgitation. MRA demonstrated aortic tortuosity, an infrarenal aortic aneurysm and aneurysms in the left renal and right internal mammary arteries. She underwent aortic root repair and aortic valve replacement. She had a background of long-standing joint pains secondary to hypermobility, easy bruising, unusual fracture susceptibility and mild bronchiectasis. She had one healthy child age 32, after which she suffered a uterine prolapse. Examination revealed mild Marfanoid features. Uvula, skin and ophthalmological examination was normal. Results: Fibrillin-1 testing for Marfan syndrome (MFS) was negative. Detection of a c.1270G > C (p.Gly424Arg) TGFBR2 mutation confirmed the diagnosis of LDS. Losartan was started for vascular protection. Conclusions: LDS is a severe inherited vasculopathy that usually presents in childhood. It is characterized by aortic root dilatation and ascending aneurysms. There is a higher risk of aortic dissection compared with MFS. Clinical features overlap with MFS and Ehlers Danlos syndrome Type IV, but differentiating dysmorphogenic features include ocular hypertelorism, bifid uvula and cleft palate. Echocardiography and MRA or CT scanning from head to pelvis is recommended to establish the extent of vascular involvement. Management involves early surgical intervention, including early valve-sparing aortic root replacement, genetic counselling and close monitoring in pregnancy. Despite being caused by loss of function mutations in either TGFβ receptor, paradoxical activation of TGFβ signalling is seen, suggesting that TGFβ antagonism may confer disease modifying effects similar to those observed in MFS. TGFβ antagonism can be achieved with angiotensin antagonists, such as Losartan, which is able to delay aortic aneurysm development in preclinical models and in patients with MFS. Our case emphasizes the importance of timely recognition of vasculopathy syndromes in patients with hypermobility and the need for early surgical intervention. It also highlights their heterogeneity and the potential for late presentation. Disclosures: The authors have declared no conflicts of interes