Plasma Cholinesterase Activity Research Articles

New Insights into Butyrylcholinesterase Activity Assay: Serum Dilution Factor as a Crucial Parameter.

Butyrylcholinesterase (BChE) activity assay and inhibitor phenotyping can help to identify patients at risk of prolonged paralysis following the administration of neuromuscular blocking agents. The assay plays an important role in clinical chemistry as a good diagnostic marker for intoxication with pesticides and nerve agents. Furthermore, the assay is also commonly used for in vitro characterization of cholinesterases, their toxins and drugs. There is still lack of standardized procedure for measurement of BChE activity and many laboratories use different substrates at various concentrations. The purpose of this study was to validate the BChE activity assay to determine the best dilution of human serum and the most optimal concentration of substrates and inhibitors. Serum BChE activity was measured using modified Ellman’s method applicable for a microplate reader. We present our experience and new insights into the protocol for high-throughput routine assays of human plasma cholinesterase activities adapted to a microplate reader. During our routine assays used for the determination of BChE activity, we have observed that serum dilution factor influences the results obtained. We show that a 400-fold dilution of serum and 5mM S-butyrylthiocholine iodide can be successfully used for the accurate measurement of BChE activity in human serum. We also discuss usage of various concentrations of dibucaine and fluoride in BChE phenotyping. This study indicates that some factors of such a multicomponent clinical material like serum can influence kinetic parameters of the BChE. The observed inhibitory effect is dependent on serum dilution factor used in the assay.

Establishing the Cholinesterase Levels in Jordan : An Investigation and Monitoring Model for Pesticides Outbreak = تحديد مستوى الكولين أستريز في الأردن : نموذج تقصي و رصد لحدوث انتشار التسمم بالمبيدات

Background Aims: To establish and validate the method used to analyze cholinesterase in blood and to establish a baseline level among Jordanians living in a heavy agricultural activity area and as well as among those living in an urban non-agricultural area. Materials and Methods: Modified Ellman procedure was used to analyze 851 and 1033 blood samples from heavy agricultural activity and urban area for cholinesterase activity in erythrocytes and Plasma. Results: sample collected from heavy agricultural activity showed low cholinesterase level average 1037U/L ± 279 and 23 U/gHb ± 7.9 compared with urban area average 1616 U/L ± 662 and 31 U/gHb ± 13 for plasma and erythrocyte respectively. The levels in workers living in heavy agriculture activity showed 52% inhibition in plasma and 41.1% in erythrocyte when compared to the established normal levels that were observed in urban area. Conclusions: Clinicians using cholinesterase for clinical diagnosis and management should be aware that baseline levels are different according to the residence of their patients.

Plasma Cholinesterase Activity in Alzheimer's Disease

Cholinesterase inhibitors (ChEIs) are not allowed to be prescribed in combination, which means that we need to select 1 of 3 ChEIs for use in a patient with Alzheimer's disease (AD). However, there is no quantitative analysis on the differences between these agents. In this article, we propose that plasma cholinesterase activity (pChE) could be used as the standard for differentiating between rivastigmine (Riv) and donepezil (Don) in the management of AD. To date, we have treated 6 patients with Riv 18 mg and 5 patients with Don 5 mg. The pChE is related to low-grade inflammation associated with AD, diabetes mellitus and lipid metabolic dysfunction. Moreover, low pChE is related to liver dysfunction. The pChE must be kept under control. We speculated that Riv is the most appropriate therapy for patients with relatively high pChE, whereas Don is best reserved for those AD patients with relatively low pChE.

Effect of pesticide exposure on immunological, hematological and biochemical parameters in thai orchid farmers- a cross-sectional study.

Various studies have found that many Thai orchid farmers used excessive amounts of pesticides without proper protective gear, but no toxicological study has been made. This cross-sectional study aimed to evaluate the immunological, hematological and biochemical statuses of these farmers. Sixty four orchid farmers and 60 controls were studied. Plasma cholinesterase activity, the percentage and absolute number of B lymphocytes (CD19+) were significantly lower in the farmers group (3966.32 ± 1165.48 U/L, 11.61 ± 4.09% and 312.26 ± 164.83 cells/mm3, respectively) as compared to those of controls (5048.85 ± 1139.40 U/L, 14.32 ± 4.23%, 420.34 ± 195.18 cells/mm3, respectively). There was a statistically significant higher level of serum IgE among the orchid farmers (0.031 ± 0.011 mg/dL vs. 0.018 ± 0.007 mg/dL) but not IgG, IgA and IgM, levels. Serum lysozyme level, lymphocyte proliferative responses to mitogens, hematological parameters and kidney function test, were not significantly different between the two groups. The liver function profiles showed significantly lower levels of albumin and serum protein in the farmer group. Thus frequent pesticide exposure resulted in subtle changes of some biological parameters. These changes, though may not be clinically significant, strongly indicated that caution in handing pesticides by these farmers is warranted.

Effects of Agricultural Management Policies on the Exposure of Black-Winged Stilts (Himantopus himantopus) Chicks to Cholinesterase-Inhibiting Pesticides in Rice Fields.

Levels of exposure to pesticides in rice fields can be significant depending on the environmental policies practiced. The aim of European Union integrated management policy is to reduce pesticide use and impact on environment. Rice fields provide an alternative breeding habitat for many waterbirds that are exposed to the pesticides used and therefore can be valuable indicators of their risk for wildlife. To evaluate integrated management success we examined exposure of Black-winged Stilts (Himantopus himantopus) to cholinesterase-inhibiting pesticides in rice fields under different types of management by measuring plasma cholinesterase activity. Cholinesterase activity was lower in birds sampled in (a) 2008 after a period of intense pesticide application, than in (b) 2005-2007 and 2011 in rice fields subject to integrated management in Doñana (SW Spain) and (c) in control natural wetlands in Spain and Morocco. During 2009 and 2010, cholinesterase activity was lower in rice fields in Doñana than in rice fields in Larache and Sidi Allal Tazi (NW Morocco). Our results suggest that integrated management successfully reduced the exposure of Black-winged Stilts to pesticides in most of the years. Care should be taken to implement mosquito and pest crop controls on time and with environmentally friendly products in order to reduce its impact on wildlife.

Measurement of cholinesterase enzyme activity before and after exposure to organophosphate pesticides in farmers of a suburb region of Mazandaran, a northern province of Iran.

Accidental toxicity by organophosphate (OP) agents may occur among farmers during spraying season due to improper use and handling. Plasma cholinesterase (ChE) activity measurement is recommended to monitor the extent of exposure to the OP agent. The aim of the current study was to measure plasma ChE activity before and after exposure with OP pesticides. This was a prospective study conducted on 36 farmers working in the farm field. The plasma ChE level was measured before spraying and 2 days and 8 weeks after spraying season and exposure to OP agent. Farmers were observed for clinical signs and symptoms of toxicity after exposure. Vertimac was the most common agent used by farmers followed by diazinon and chlorpyrifos. The plasma ChE level significantly decreased after exposure by over 50%. The level returned to preexposure level after 8 weeks. Exposure to OP pesticide is a major concern in the developing countries. More than 50% reduction in the plasma ChE activity after spraying is an alarming message for health-care system and policy makers. Furthermore, workplace evaluation, serial ChE monitoring, and appropriate training and education to exposed individuals would be initial important steps to avoid the toxicity or reduce the severity of poisoning.

Plasma cholinesterase activity of rats, western grey kangaroos, alpacas, sheep, cattle, and horses.

Plasma cholinesterase activity levels of various species may be of interest to toxicologists or pathologists working with chemicals that interfere with the activity of plasma cholinesterase. We used a pH titration method to measure the plasma cholinesterase activity of six mammalian species. Plasma cholinesterase activity varied up to 50-fold between species: sheep (88 ± 45 nM acetylcholine degraded per ml of test plasma per minute), cattle (94 ± 35), western grey kangaroos (126 ± 92), alpaca (364 ± 70), rats (390 ± 118) and horses (4539 ± 721). We present a simple, effective technique for the assay of plasma cholinesterase activity levels from a range of species. Although labour-intensive, it requires only basic laboratory equipment.

Effects of acute organophosphate poisoning on pituitary target gland hormones at admission, discharge and three months after poisoning: A hospital based pilot study.

Background:Organophosphate compound (OPC) poisoning is common in the developing countries such as India. The acute and later effects of OPC poisoning on pituitary and target gland hormones is largely unknown.Materials and Methods:This prospective study was conducted at Postgraduate Institute of Medical Education and Research between January 2012 and March 2013. Fourteen patients (8 males, age 18-50 years) with acute OPC poisoning were included in the study based on the history and clinical features, documented decreased in plasma cholinesterase activity or presence of the OPC in gastric lavage/blood samples. The hormonal parameters were done at baseline, at the time of discharge and at three months of follow-up.Results:A total of 14 patients out of 46 with the mean age of 30.1 ± 10.3 years were finally eligible for the study. Hormonal alterations at admission were similar to sick euhormonal syndrome. Overall 7 of them had nine hormonal deficits at three months of follow up, 4 having sub normal basal cortisol level and two each had low testosterone and growth hormone and only one had thyroxine deficiency.Conclusion:Acute organophosphate poisoning results in endocrine dysfunction akin to sick euhormonal syndrome. However, in a small subset of patients, varying level of hormonal insufficiency may occur either at admission or later. These observations need re-validation in a larger group of patients with specific OPC.

Effectiveness of High Dose Pralidoxime for Treatment of Organophosphate Poisoning

Background: For effective treatment of organophosphate (OP) poisoning, development of a standardized protocol with flexible dose regimen for atropine and pralidoxime is an essential step. In this study, we aimed to assess the protocol devised in our setting; Bach Mai Hospital Poison Treatment Center, for treatment of OP poisoning that included a higher dose regimen of pralidoxime (2PAM). Methods: A protocol for treatment of OP poisoning was developed during 1995 to 1996, which included an atropinization scoring scale and a modification of 2PAM dose regimen. In this study, OP poisoned patients who were treated during 1997 to 2002 with the new protocol (study group or cases) were compared with historical control group which included OP poisoned patients treated between 1993 and 1994 prior to establishment of the new protocol. Results: One-hundred and eight cases and 54 controls were included. The cases and controls were not significantly different according to age, gender and plasma cholinesterase activity on admission from each other. There was no significant difference of mean duration of 2PAM therapy between the two groups. The controls received mean total 2PAM dose of 7.2±4.1 g, while the patients in the study group received 20.0±12.7 g which was 2.77 times higher than the dose for control group (P<0.001). Patients in the study group received significantly lower doses of atropine (100.2±119.1 vs. 231.8±225.5, P<0.001). Patients in the study group required a shorter duration of hospital stay compared to controls (6.2±4.8 vs. 8.2±5.8, P=0.035). In addition, morality rate decreased significantly (P=0.004) from 13% to 1.9% by application of the new protocol. Conclusion: The new protocol was more effective for patients with OP toxicity as it reduced the morbidities and mortality. A flexible regimen of 2PAM therapy for OP poisoning is recommended to be implemented.

Chlorpyrifos and cypermethrin induce apoptosis in human neuroblastoma cell line SH-SY5Y.

Our previous in vivo studies showed that chlorpyrifos (CPF) and cypermethrin (CM) in a mixture dermally administered, strongly inhibited cholinesterase activity in plasma and the brain and were very toxic to the rat central nervous system. In this work, the mechanisms of neurotoxicity have not been elucidated. We used human undifferentiated SH-SY5Y cells to study mechanisms of pesticide-induced neuronal cell death. It was found that chlorpyrifos (CPF) and its mixture with cypermethrin (CPF+CM) induced cell death of SH-SY5Y cells in a dose- and time-dependent manner, as shown by MTT assays. Pesticide-induced SH-SY5Y cell death was characterized by concentration-dependent down-regulation of Bcl-2 and Bcl-xL as well as an increase in the caspase 3 activation. Pan-caspase inhibitor Q-VD-OPh produced a slight but significant reversal effect of pesticide-induced toxicity indicating that the major caspase pathways are not integral to CPF- and CPF+CM-induced cell death. Furthermore, signal transduction inhibitors PD98059, SL-327, SB202190, SP600125 and mecamylamine failed to attenuate pesticides effect. Atropine exhibited minimal ability to reverse toxicity. Finally, it was shown that inhibition of TNF-α by pomalidomide attenuated CPF-/CPF+CM-induced apoptosis. Overall, our data suggest that FAS/TNF signalling pathways may participate in CPF and CPF+CM toxicity.

Physiological, biochemical and histological alterations induced by administration of imidacloprid in female albino rats

Imidacloprid, a neonicotinoid the newest class of major insecticide has outstanding potency and systemic action for crop protection against piercing and sucking insects pests and also highly effective for control of flea on cats and dogs. The effect of oral administration of two doses of imidacloprid 10 and 20mg/kg/day for 60days on biochemical parameters, histopathology and protein profile of female albino rat was assessed. Average feed intake was significantly reduced (P<0.01) at 20mg/kg/day. Relative weight of heart and spleen decreased significantly (P<0.05) at higher dose level. Non significant increase in alanine aminotransferase (ALT), aspartate aminotransferase (AST), acid phosphatase (ACP), alkaline phosphatase (AKP) activity was observed in both the imidacloprid treated groups. There was significant decrease (P<0.01, P<0.05) in acetyl cholinesterase (AChE) activity in plasma and brain of both the imidacloprid treated groups. Microscopically, liver tissue of rats treated with higher dose of imidacloprid showed marked dilation and congestion of central vein and degeneration of hepatocytes. The exposure to imidacloprid produced histopathological changes that could be correlated with changes in the biochemical profile of female albino rats. The blood plasma proteins were examined by SDS PAGE. There was no diagnostic difference in the pattern of plasma protein profile of control and treated rats. Based on the present physiological, biochemical and histological studies it is evident that imidacloprid did not produce any significant effects at 10mg/kg/day dose but induced toxicological effects at 20mg/kg/day to female rats.

Plasma cholinesterase activity as diagnostic marker for systemic inflammation

Systemic inflammation is a generalized response to internal or external inflammatory stimuli often resulting in multiple organ failure. Therefore, early diagnosis of systemic inflammation would be of great therapeutic and prognostic importance. Various inflammation biomarkers have been used in clinical and experimental practice, but a definitive diagnostic tool for an early detection of systemic inflammation remains to be identified. The neurotransmitter acetylcholine (Ach) has been shown to play an important role in the inflammatory response. Serum cholinesterase (butyrylcholinesterase (BChE)) is synthesized in the liver and acts as the major Ach hydrolyzing enzyme in plasma. Hence, BChE activity has been widely used as a biomarker for liver function. However, the role of this enzyme in the inflammatory pathomechanism has not yet been fully understood. Here, we describe a strong correlation between the BChE activity and the systemic inflammatory response.

Prognostic significance of various biochemical parameters in acute organophosphorus poisoning.

Background:Organophosphorus (OP) compounds are a heterogeneous group of insecticides widely used in agricultural industry. These OP compounds are likely to have more adverse effects in developing countries like India due to its easy availability and less awareness which results in high morbidity and mortality.Aims and objectives:1. To estimate plasma cholinesterase, amylase, lipase and, creatine phosphokinase (CPK) in acute OP poisoning. 2. To correlate these biochemical parameters with plasma cholinesterase levels in OP poisoning. 3. To determine the use of a biochemical marker in predicting the severity of acute OP poisoning.Materials and Methods:A hospital based observational study was conducted on 53 subjects who have clinically diagnosed of acute OP poisoning and admitted in emergency unit of a tertiary care rural hospital. Subjects of either gender of all age-groups were included in the study. On admission, plasma cholinesterase, serum amylase, lipase and CPK were measured. Based on plasma cholinesterase activity at the time of admission, subjects were divided into three groups. Group I-having 20-50% of plasma cholinesterase activity; Group II-10-20% of plasma cholinesterase activity; and group III-<10% of plasma cholinesterase activity.Results:Serum amylase, lipase and CPK were negatively correlated with plasma cholinesterase levels. Serum amylase showed statistically significant negative correlation with plasma cholinesterase. Serum amylase showed the highest diagnostic accuracy for assessing severity of poisoning followed by CPK and Lipase.Conclusion:OP poisoning is associated with hyperamylasemia. Serum amylase, lipase and CPK can be used as an additional prognostic indicator with plasma cholinesterase levels. Serum amylase could be considered as a better predictor of severity followed by CPK and lipase.

Characterization of plasma cholinesterase in rabbit and evaluation of the inhibitory potential of diazinon

Several studies indicate that more than one cholinesterase form may be present in the blood of mammals. In this study the predominant plasma cholinesterase activity, the physiological cholinesterase activity as well as cholinesterase sex-dependent changes in non-exposed individuals of rabbit have been established. Plasma cholinesterase was characterized using three substrates (acetylthiocholine iodide, propionylthiocholine iodide, and S-butyrylthiocholine iodide) and three cholinesterase inhibitors (eserine sulfate, BW284C51 and iso-OMPA). The results indicated that propionylthiocholine was the preferred substrate by plasma cholinesterase followed by acetylthiocholine and butyrylthiocholine, and the predominant enzymatic activity was acetylcholinesterase. Physiological plasma cholinesterase activity was 198.9±5.8nmol/min/ml for male and 205.2±5.0nmol/min/ml for female using acetylthiocholine as substrate. Thus, sex had no significant effect on the physiological cholinesterase activity (p>0.05). In addition, the in vivo and in vitro sensitivity of plasma cholinesterase to diazinon was also investigated. In rabbits exposed to single doses of diazinon (25 or 125mg/kg) the higher inhibitions of plasma cholinesterase were reached 9h after oral administration (53% and 87% inhibition, respectively). Cholinesterase activity significantly recovered up to values similar to pre-administration between 3 and 7d depending on the administered dose and sex of the animals. Plasma cholinesterase activity decreased to 24%, 53% and 74% of the initial activity at 9h of in vitro exposure to 1.25, 3.13 and 6.25mg/l of diazinon, respectively, and it remained steadily depressed throughout the experimental period (10d). This study has demonstrated the sensitivity of cholinesterase activity in plasma of rabbits following both in vivo and in vitro exposure to sub-lethal concentrations of diazinon.

Plasma cholinesterase activity in children with infective endocarditis

Objectives: Although pre-existing heart disease in children is the most frequent predisposing factor for infective endocarditis (IE), we report 6 children of IE with no apparent preexisting cardiac disease. Patients and Methods: Our study included six patients with acquired infection from central catheter; the microbial pathogens were Streptococcus viridans (n=3) and Staphyloccocus aureus (n=3). The diagnosis of IE was based on positive blood culture (2 positive cultures of blood samples drawn >12 hours), evidence of endocardial involvement (positive ECHO), measuring raised erythrocyte sedimentation rate and plasma cholinesterase (PChE) activity. We measured PChE activity (µmol min -1 ml -1 ) in children with IE (group A, n=6) and in IE-free children (group B, n=10). For determination of PChE activity vein blood samples were collected and stored at -20°C until analyzed. PChE activity was determined by the spectrophotometric method of Ellman using butyryltiocholine as the substract (Sigma Chemical Co., St.Luis, Mo, USA). Statistical analysis was made by Student’s t-test. Results: In group A of examined children with IE we measured decreased PChE activity (1.89 ± 0.24) relation to patients of control group B (3.97 ± 0.20). Conclusion: Our study indicates that PChE activity can also be an important parameter for the diagnosis of IE.

Pharmakogenetik

Pharmacogenetics deals with hereditary factors which influence the pharmacodynamics and pharmacokinetics of drugs leading to individual diverse reactions. Also in anesthesiology differences in the pharmacogenetics of patients can lead to relevant alterations in the pharmacodynamics of drugs. This article provides a summary of polymorphisms relevant to commonly used anesthetic agents and the clinical relevance in patients treated with these compounds. It describes the possibilities, the problems and limits of pharmacogenetic diagnostics and therapy and explains how this follows the target of individualized medicine. This article describes in detail the alterations in pharmacodynamics and pharmakokinetics relevant for anesthesia and their clinical significance. Based on the results of current studies, an overview of the most important drugs in anesthesiology with significant polymorphisms is given. These include opioids, muscle relaxants, volatile anesthetic agents, non-steroidal anti-inflammatory drugs (NSAIDs), benzodiazepines, antiemetics and cardiovascular drugs as well as platelet aggregation inhibitors, anticoagulants and the so-called new oral anticoagulants. Genetic alterations can lead to substantial modifications in the effectiveness of drugs. Genetic alterations of opioid receptors and the enzyme cytochrome P450 (CYP) 2D6 can result in a failure of analgesia after administration of opioids. Alterations in plasma cholinesterase activity are associated with a prolonged effectiveness of muscle relaxants. Polymorphisms in ryanodine receptors can contribute to the development of the feared MH in patients after administration of volatile anesthetics or succinylcholine. The study results presented here emphasize that these days knowledge on pharmacogenetics should not be missing in modern induction of anesthesia. In the future a blood sample could enable physicians to identify pharmacologically relevant markers. And these could guide the decision on the prescription of drugs and their appropriate dose, in order to achieve the lowest risk of side effects and the highest effectiveness of the active substance.

Plasma cholinesterase activity in children with infective endocarditis

Objectives: Although pre-existing heart disease in children is the most frequent predisposing factor for infective endocarditis (IE), we report 6 children of IE with no apparent preexisting cardiac disease. Patients and Methods: Our study included six patients with acquired infection from central catheter; the microbial pathogens were Streptococcus viridans (n=3) and Staphyloccocus aureus (n=3). The diagnosis of IE was based on positive blood culture (2 positive cultures of blood samples drawn >12 hours), evidence of endocardial involvement (positive ECHO), measuring raised erythrocyte sedimentation rate and plasma cholinesterase (PChE) activity. We measured PChE activity (µmol min -1 ml -1 ) in children with IE (group A, n=6) and in IE-free children (group B, n=10). For determination of PChE activity vein blood samples were collected and stored at -20°C until analyzed. PChE activity was determined by the spectrophotometric method of Ellman using butyryltiocholine as the substract (Sigma Chemical Co., St.Luis, Mo, USA). Statistical analysis was made by Student’s t-test. Results: In group A of examined children with IE we measured decreased PChE activity (1.89 ± 0.24) relation to patients of control group B (3.97 ± 0.20). Conclusion: Our study indicates that PChE activity can also be an important parameter for the diagnosis of IE.

Characterization of plasma cholinesterase from the White stork (Ciconia ciconia) and its in vitro inhibition by anticholinesterase pesticides

Blood plasma cholinesterase (ChE) activity is a sensitive biomarker of exposure to organophosphorus (OP) and carbamate (CB) insecticides in vertebrates. Several studies indicate that more than one ChE form may be present in blood of birds. In this study the predominant ChE activity (acetylcholinesterase – AChE– or butyrylcholinesterase – BChE–), the range of ChE activity as well as ChE age-dependent changes in non-exposed individuals of White stork (Ciconia ciconia) have been established. The in vitro sensitivity of ChE to OP and CB insecticides such as paraoxon-methyl, carbofuran and carbaryl was also investigated. Plasma ChE was characterised using three substrates (acetylthiocholine iodide, propionylthiocholine iodide, and S-butyrylthiocholine iodide) and three ChE inhibitors (eserine sulphate, BW284C51 and iso-OMPA). The results indicated that propionylthiocholine was the preferred substrate by plasma cholinesterase followed by acetylcholine and butyrylcholine and the predominant enzymatic activity in plasma of White storks was BChE. Normal plasma BChE activity in White stork was 0.32±0.01μmol/min/ml for adults and 0.28±0.03μmol/min/ml for juveniles. So, the age had no significant effect on the range of BChE activity. The study on the in vitro inhibitory potential of tested anticholinesterase pesticides on plasma ChE activity revealed that paraoxon-methyl is the most potent inhibitor followed by carbofuran and finally by carbaryl. The percentage of in vitro plasma ChE inhibition was observed to be similar between adults and juveniles.

Plasma cholinesterase activity in hepatic diseases

Plasma cholinesterase activity (ChE) may vary in some pathological circumstances. We studied the changes in activity of this enzyme according to the type of liver injury, to assess the interest of this parameter in the diagnosis of liver diseases. Our study was performed on 102 patients with different liver diseases and 53 healthy controls. The ChE activity was lower in patients compared to control group (p < 0.0001), and more pronounced in cirrhotic patients compared to those suffering from hepatitis. Elevated activities of AST, ALT, GGT and ALP and bilirubinemia, and decreased albuminemia were noted in patients compared to controls (p < 0.001). Hypoalbuminemia was significantly important in cirrhotic patients compared to those suffering from cholestasis or hepatitis. A correlation between ChE and bilirubin, albumin and serum protein was found in patients with cirrhosis or those with chronic hepatitis. A significantly lower activity of ChE was found in patients with hepatic insufficiency (HI). In case of suspicion of HI, the prescription of ChE activity could guide or confirm the diagnosis of the impairment.

Sugammadex Dosing in Bariatric Patients

We read with interest the article by Llauradó et al .1focusing on the efficiency of ideal body weight–adjusted sugammadex dosing in patients undergoing bariatric surgery. The authors report a high incidence of slow responders and outliers leading to a potential risk of recurarization; they consider ideal body weight–adjusted dosing of sugammadex as unsafe. However, we feel that a significant lack of clarity in both design and methods makes it difficult to draw any conclusion from that study.First, patients in the deep-block group had a posttetanic count (PTC) ⩽ 2, thus including also those with no response to PTC. According to the good clinical research practice for pharmacodynamic studies of neuromuscular blocking agents, deep block is defined as no response to train-of-four stimulation but at least one response to the 15 PTC stimulations.2This definition is used because PTC1 is the deepest neuromuscular block that can be precisely defined; as soon as no response to PTC is detectable, neuromuscular block can no longer be quantified. Indeed, it may be close to return of the first PTC response, but it may also be much more intense, with no return to the first PTC answer for a long period. This heterogeneous group of neuromuscular blockade with no response to PTC is summarized as intense blockade.2Although the recommended dose of sugammadex to antagonize moderate or deep block is 2 and 4 mg/kg, respectively, only a few studies focused on sugammadex dosing for intense neuromuscular block, i.e. , when no response to PTC can be detected.3,4They proposed a dose between 8 and 16 mg/kg depending on the elapsed time interval between rocuronium injection and start of reversal. In the present study, however, these patients were also treated with 4 mg/kg ideal body weight sugammadex. Thus, independently of whether sugammadex dosing is based on real or ideal body weight, it was significantly underdosed in patients with no response to PTC. This may have contributed to the “outliers” observed by Llauradó et al . Second, all patients in the present study had either a PTC ⩽ 2 or a train-of-four count ≥ 2. Not 1 of the 120 patients included in this observational study has a neuromuscular block level in between, that is, corresponding to 3–15 PTC or a train-of-four count of 1. This is at least surprising and let suppose an active control rather than a real observation. Third, induction of anesthesia was not standardized; some patients received succinylcholine, whereas others did not. This, however, does not facilitate the interpretation of the results. How can the authors exclude that some of the patients in their study were “slow responders” or “outliers” because of impaired plasmacholinesterase activity leading to slow succinylcholine metabolism rather than a delayed response to sugammadex-induced reversal? Fourth, there may be a bias in the patient’s group assignment. According to the authors, the level of neuromuscular block at the end of surgery determined whether the patients were assigned to deep or moderate block group. However, the total dose of rocuronium was identical in both groups, and surgical time was slightly longer in the deep-block group. Thus, despite the same dose of rocuronium and somewhat longer surgical procedure, 43 patients had a profound block, whereas the remaining 77 patients had a shorter duration but only a moderate neuromuscular block. Interindividual variability to neuromuscular blocking agents is large and the group assignment let suppose that patients more “resistant” to rocuronium were assigned to the moderate group, whereas patients more “sensitive” to rocuronium were assigned to the deep group. Finally, if the train-of-four ratio did not reach 0.9 within 2 or 3 min, respectively, a second dose of sugammadex was given. This, however, did not allow to draw any conclusions on either the risk of recurarization or the time course of an ideal body weight–adjusted sugammadex dosing.Denis Schmartz, M.D.,*Philippe Guerci, M.D., Thomas Fuchs-Buder, M.D., Ph.D.*CHU de Nancy, Hôpital Brabois Adultes, Institut Lorrain du Coeur et des Vaisseaux Louis Mathieu, France. d.schmartz@chu-nancy.fr