over decades , the incidence of obesity has tripled , and number of obese patients undergoing surgery has also increased . diseases associated with obesity such as diabetes , hypertension , cardiopulmonary diseases and obstructive sleep apnoea reduce the margin of safety of anaesthetic drugs . body composition , regional blood flow and tissue affinity alter distribution of drugs in these patients posing a significant challenge to anaesthesiologist . vecuronium is an intermediate acting neuromuscular blocker ( nmb ) mainly distributed in lean body mass . hence , vecuronium dose based on the real body weight ( rbw ) in obese patients results in relative over dosing , with significantly increased duration of action and slower spontaneous recovery , compared to normal weight patients . objective neuromuscular ( nm ) monitoring allows clinicians for accurate use of reversal agents . ensuring adequate recovery from nmb is mandatory to prevent any residual block and its associated complications such as aspiration , hypoventilation and airway obstruction secondary to impaired pharyngeal and laryngeal function , attenuation of hypoxic ventilatory response and unpleasant symptoms of muscle weakness this study was designed primarily to compare the efficacy of neostigmine in reversing the nmb , induced by vecuronium dose based on the patient 's rbw in normal weight , overweight and obese female patients . time taken for recovery of nm function following administration of neostigmine to train of four ( tof ) ratios of 0.5 , 0.7 and 0.9 were studied . the time taken from administration of the last dose of vecuronium to spontaneous recovery of twitch height ( t1 ) to 25% of control ( dur 25% ) in each group was also noted . this prospective cross sectional study was conducted between july 2009 and july 2011 , after approval of the protocol by institutional ethics committee . three groups of 20 patients each were recruited , after their written informed consent for the study . grouping of patients was based on body mass index ( bmi = weight [ kg]/height [ m ] ) , as group i = normal weight ( bmi 18 to < 25 ) , group ii = overweight ( bmi 25 to < 30 ) and group iii = obese ( bmi  30 ) . the primary end point of the study was time taken for nm function to reach a tof of 0.9 in all the three groups . a sample size of 20 to ensure at least a mean difference of 2 min between two groups to represent 90% power and 5% type 1 error was arrived at . female patients belonging to american society of anaesthesiologists ( asa ) physical status 1 and 2 , aged between 18 and 60 years , posted for elective surgery under general anaesthesia were included in the study . pregnant and lactating women , patients with nm disorders , hepatic and renal disease or on any drugs known to interact with nmb were excluded from the study . all patients were pre - medicated with tablet ranitidine 150 mg hs and tablet alprazolam 0.25 mg hs on the previous day of surgery , with overnight fasting . in the operation theatre , electrocardiogram , non - invasive blood pressure , acceleromyographic tof monitor ( tof guard , organon technika laboratories ) along with surface temperature probe was attached to the hand . after pre - oxygenation , they were induced with iv fentanyl 2 mcg / kg , followed by iv propofol 2 mg / kg or till the loss of verbal contact . later , ulnar nerve was stimulated at the wrist with supra - maximal stimuli of 0.2 ms duration , delivered in a tof mode at 2 hz every 15 s and contraction of the ipsilateral adductor pollicis muscle was measured using acceleromyography . the t1 of tof and tof ratio measured at the end of control stimulation was regarded as the baseline value . patients were ventilated with 40% oxygen , 60% nitrous oxide and uniform concentration of isoflurane in all groups . airway was secured with adequate size cuffed endotracheal tube after 3 min of vecuronium administration . repeat doses of vecuronium 1 mg was given at 45 min after first dose and then at every 30 min , based on institutional practice , till the completion of surgery . during recovery , nm block was monitored using acceleromyographic tof by assessing contraction of adductor pollicis muscle . at dur 25% , iv neostigmine 40 mcg / kg and glycopyrrolate 10 mcg / kg were given to reverse the nmb . demographic details and variables including ( a ) dur 25% ( b ) time taken for facilitated recovery to tof ratios of 0.5 , 0.7 and 0.9 following neostigmine administration ( c ) total number of doses of vecuronium ( d ) duration of surgery were measured . the statistical software spss18.0 ( pasw statistics , 18.0 , spss inc . , chicago , il , usa ) was used for the analysis of the data . results on continuous measurements were presented on mean  standard deviation ( sd ) and results on categorical measurements were presented in a number ( % ) . to measure the significance between the groups overweight and obese patients were found to be more in older age groups ( age in years in group i [ 33.80  12.73 ] , group ii [ 42.65  12.11 ] and group iii [ 45.30  9.97 ] ) with statistical significance ( p = 0.008 ) . asa grading , baseline vital parameters ( heart rate , blood pressure and oxygen saturation ) and skin temperature were comparable in all three groups . statistically significant difference in bmi was observed among the groups , which validate the grouping [ table 1 ] . comparison of bmi ( kg / m ) among three groups dur 25% was significantly longer in overweight ( 30.10  5.91 min ) and obese patients ( 28.80  8.91 min ) when compared with normal weight ( 22.75  3.98 min ) patients ( p = 0.002 and 0.014 respectively ) . time taken for recovery of tof to 0.5 following reversal was comparable in all three groups . recovery of tof ratio to 0.7 was delayed in obese ( 9.82  3.21 min ) as compared to normal weight group ( 7.50  2.52 min ) with p = 0.047 . furthermore , recovery of tof to 0.9 was delayed in both overweight ( 12.18  4.29 min ) and obese patients ( 13.78  4.30 min ) , which was statistically significant [ table 2 ] with p = 0.047 and 0.001 respectively . comparison of spontaneous recovery of t1 and tof ratio ( min ) among three groups mean number of repeat doses of vecuronium received by groups i , ii and iii were 3.75  2.57 , 3.80  2.22 and 3.90  2.25 respectively . they were statistically similar in all three groups with p = 0.979 [ figure 1 ] . duration of surgery was comparable among all three groups with p = 0.916 [ table 3 ] . comparison of number of repeat doses of vecuronium comparison of total duration ( min ) of surgery among three groups the physiological and anthropometric changes associated with obesity alter the pharmacokinetic properties of most drugs . obese individuals are often excluded from clinical trials despite the growing recognition of the impact of obesity on pharmacokinetic and pharmacodynamic properties of the drugs . dosing information in the package inserts is usually based on the kilogram of rbw , which can result in incorrect doses when applied to the obese patients . previous studies have demonstrated that obese patients have prolonged duration of action when vecuronium is given based on rbw . demonstrated that vecuronium had prolonged duration of action in obese patients probably due to overdose and impaired clearance . our study was undertaken to evaluate whether these factors are likely to affect the neostigmine induced recovery of nm block also . we studied recovery indices in 60 patients when vecuronium and neostigmine were given based on rbw . standard anaesthetic technique included the uniform concentration of isoflurane in all groups . in the study by ingrande and lemmens obese subjects given 0.6 minimum alveolar concentration of isoflurane for surgery lasting 2 - 4 h showed similar recovery profiles as non - obese subjects . in addition , the time constant for isoflurane to reach equilibrium with adipose tissue is approximately 2110 min , much longer than most surgical cases . this property , coupled with low adipose tissue blood flow , diminish the effect of excess adiposity on isoflurane distribution and recovery . relatively older patients in obese ( 45.3  9.97 years ) and overweight ( 42.65  12.11 years ) groups in our study were considered clinically not significant , as all patients enrolled were < 60 years of age . mccarthy et al . noted duration of action of vecuronium and recovery indices are prolonged only in elderly patients ( 80  4.6 years ) and not in younger ( 34  11.1 years ) and middle aged ( 60  5.8 years ) group . vecuronium has weak to moderate lipophilic property due to its steroidal structure and is mainly distributed in lean tissues . therefore , when vecuronium is given based on rbw , it results in over dosing and prolonged duration of action . in our study , dur 25% of control was significantly longer in the overweight ( mean , sd [ range ] ; 30.10 [ 1940 min ] ) and obese ( 28.8 [ 1245 min ] ) as compared to normal weight patients ( 22.75 [ 1630 min ] ) . overweight and obese patients took longer time ( mean [ 49.3 min ] and [ 68.4 min ] respectively ) to recover as compared to normal weight patients ( 41 min ) . the relatively longer recovery time in their study could be because of single dose administration of vecuronium with short duration of surgery . however , their study did not address the impact of multiple doses required in long duration surgeries . in our study , induction dose of vecuronium ( 0.1 mg / kg ) used was based on rbw . literature is limited on specific recommendations for repeat doses of vecuronium in obese and overweight patients . however , in view of longer duration of surgery , repeat doses of vecuronium 1 mg were used uniformly in all patients as per our routine institutional protocol , with adequate clinical nm blockade . the resultant dose was much lower than the dose calculated based on rbw in obese and overweight patients . fisher and rosen 's pharmacokinetic and pharmacodynamic modelling attributes the large initial dose of vecuronium to slow recovery . reported in their study that dur 25% was longer in obese ( 14.6  6.7 min ) as compared to the control group ( 6.9  1.9 min ) . vecuronium noted an increase in time to recover to 5 - 25% of t1 in obese patients ( 14.9  4.0 min ) as compared to control group ( 10.0  1.7 min ) and attributed this to a large total dose of vecuronium . reversal time is determined by two processes which include direct antagonism by anticholinesterase and spontaneous recovery from the elimination of the drug from the plasma . the optimum time to administer neostigmine for antagonizing vecuronium induced nm blockade is found to be during spontaneous recovery of t1 between 1% and 10% . noted that highest nm transmission recovery occurs when neostigmine is administered at 25% to 50% recovery of twitch height . in our study , reversal was administered at 25% recovery of t1 . we noted that time taken for recovery of tof to 0.5 following reversal was comparable in all three groups . however , recovery to tof ratio of 0.7 was delayed in obese ( 9.82  3.21 min ) as compared to normal weight group ( 7.50  2.52 min ) . furthermore , recovery of tof to 0.9 was delayed in both overweight ( 12.18  4.29 min ) and obese patients ( 13.78  4.30 min ) which was statistically significant . suzuki et al . found that time required to recover to tof ratio of 0.5 and 0.7 were comparable between the groups and the late phase of recovery to 0.9 was delayed in overweight ( 3.328.5 min ) and obese groups ( 13.541.0 min ) . reversal effect of neostigmine usually appears within about 12 min and the maximum effect occurs in about 610 min . it is therefore considered that the early facilitated recovery to a tof ratio of 0.5 observed in overweight and obese patients may be attributed to competitive antagonism to vecuronium at the nm junction ( nmj ) because of increased acetylcholine concentration . however , once the true cholinesterase at the nmj is totally inactivated , additional neostigmine produces no further increase in available acetylcholine . recovery to tof ratio of 0.7 and 0.9 was delayed in overweight and obese , which may represent a balance between spontaneous recovery ( elimination of drug from plasma ) from overdosed vecuronium induced block and the waning reversal effect of neostigmine . clinical parameters used for nm recovery such as patient 's ability to maintain a 5 s head lift and hand grip maybe present at tof ratio of 0.7 and does not ensure complete recovery . clinical evidence clearly indicates that low levels of residual paralysis corresponding to tof ratio 0.70.9 may be harmful . therefore , the delay in recovery between tof ratio of 0.7 - 0.9 in overweight and obese patients in our study has important clinical relevance for patient safety . baurain et al . studied the conditions to optimize the reversal action of neostigmine upon vecuronium induced nmb and concluded that in order to obtain the highest nm transmission recovery ( tof of 0.9 ) , 40 mcg / kg dose of neostigmine has to be given at 2550% recovery of twitch height . increasing the dose of neostigmine to 80 higher doses of neostigmine ( 50 g / kg ) can antagonize the block more rapidly than smaller doses ( 5 , 10 , 20 g / kg ) . to reverse the profound block , maximum dose of neostigmine ( 7080 g / kg ) anticholinesterases exhibit a ceiling effect when used in large doses and recovery will not be accelerated with further increase in dose of neostigmine . kopman and eikermann used low dose of neostigmine ( 1520 g / kg for tof count of four and 4050 g / kg for tof count of two or three ) to minimise potential cardiovascular and respiratory side effects when nmb was not intense . the recommended dose of neostigmine is 4080 g / kg , not exceeding a total of 5 mg . in obese subjects , recovery of nm function after reversal with neostigmine is found to be incomplete as compared to normal weight subjects . further studies are recommended to assess the dose of neostigmine in overweight and obese patients in order to obtain safe anaesthetic outcome . sugammadex is a specifically designed gamma cyclodextrin and selective relaxant binding drug that rapidly reverses the effects of rocuronium and vecuronium induced block . however , cost and non - availability may still be considered as major limiting factors for its widespread use . decisions with regard to dosage and timing of neostigmine in overweight and obese patients require clinical and nm monitoring for a safe recovery . further studies are required for optimising the dosing of neostigmine in obese and overweight patients . when vecuronium is administered based on rbw , the total reversal time by neostigmine 40 mcg / kg , is prolonged in overweight and obese patients compared to normal weight patients . early recovery of tof to 0.5 was comparable in all three groups , recovery of tof to 0.7 was delayed in obese and tof to 0.9 was delayed in both obese and overweight patients . this finding of incomplete nm recovery has important clinical significance in view of associated complications . vecuronium induction dose , based on rbw in obese and overweight groups has longer duration of action with slower spontaneous recovery ( dur 25% ) . clinical evaluation of adequate recovery should be supplemented with objective monitoring of nm function for patient safety .
background and aims : obese patients are more vulnerable to residual neuromuscular block ( nmb ) and its associated complications in the post - operative period . 
 this study was carried out to compare neostigmine induced reversal of vecuronium in normal weight , overweight and obese female patients , objectively using neuromuscular ( nm ) monitoring.methods:twenty female patients each belonging to normal weight , overweight and obese , based on body mass index , requiring general anaesthesia were recruited for this prospective cross sectional study . 
 nmb was induced with vecuronium ( 0.1 mg / kg ) dose based on patient 's real body weight ( rbw ) and monitored using acceleromyographic train of four ( tof ) . 
 all patients received neostigmine 40 g / kg and glycopyrrolate 10 g / kg at 25% of spontaneous recovery of first twitch height ( t1 ) of tof ( dur 25% ) and were allowed to recover to tof ratio of 0.9 . 
 statistical analysis was done using analysis of variance test.results:recovery of tof ratio to 0.5 was comparable in all three groups . 
 recovery of tof ratio to 0.7 was delayed in obese ( 9.82  3.21 min ) compared with normal weight group ( 7.50  2.52 min ) . 
 recovery of tof to 0.9 was significantly delayed in both overweight ( 12.18  4.29 min ) and obese patients ( 13.78  4.30 min ) . 
 dur 25% was significantly longer in overweight ( mean , standard deviation [ range ] ; 30.10 [ 1940 min ] ) and obese ( 28.8 [ 1245 min ] ) compared with normal weight patients ( 22.75 [ 1630 min]).conclusion : in overweight and obese patients , when vecuronium induction dose is based on rbw , neostigmine induced recovery of nmb is delayed in late phases ( tof 0.7 - 0.9 ) , which may result in vulnerability for associated complications of incomplete recovery . ensuring safe recovery 
 thus requires objective nm monitoring .