Comparison of adjuvant pharmaceuticals for caudal block in pediatric lower abdominal and urological surgeries: A network meta-analysis.

STUDY OBJECTIVE: Caudal block helps relieve pain after sub-umbilical surgery in pediatric patients; however, the duration for which it exerts its analgesic effect is limited. The addition of certain adjuvant agents to local anesthetics (LAs) that are used to administer caudal block can prolong postoperative analgesia. Therefore, we aimed to compare the efficiencies and side effects of caudal adjuvants in the settings of pediatric lower abdominal and urological surgeries. DESIGN: A network meta-analysis (NMA). PATIENTS: One hundred and twelve randomized controlled trials (RCTs) involving 6800 pediatric patients were included in the final analysis. INTERVENTIONS: Different adjuvant agents, namely clonidine, dexamethasone, dexmedetomidine, fentanyl, ketamine, magnesium, midazolam, morphine, neostigmine, and tramadol. MEASUREMENTS: The primary outcome was the duration of analgesia. The secondary outcomes included the requirement for additional analgesia, analgesic consumption, and postoperative complications. The effects and rankings were evaluated using NMA and the surface under the cumulative ranking curve scores, respectively. RESULTS: Neostigmine, dexmedetomidine, and dexamethasone were found to be the three most effective adjuvants that prolong the duration of analgesia for caudal block, and these adjuvants extended this duration by 8.9 h (95% confidence interval [CI], 7.1-10.7), 7.3 h (95% CI, 6.0-8.6), and 5.9 h (95% CI, 4.0-7.7), respectively. Caudal neostigmine was associated with an increase in the incidence of postoperative nausea and vomiting, whereas dexmedetomidine and dexamethasone showed no postoperative complications. CONCLUSIONS: This NMA provided evidence and suggested that dexmedetomidine and dexamethasone may be the most beneficial adjuvant pharmaceutics adding to LAs for caudal block in children. However, given the off-label status of caudal dexmedetomidine and dexamethasone, further high-quality RCTs are still warranted, especially to determine whether delayed neurological complications will occur.

Neostigmine Attenuates Proinflammatory Cytokine Expression in Preoptic Area but Not Choroid Plexus during Lipopolysaccharide-Induced Systemic Inflammation.

The study was designed to examine whether the administration of neostigmine (0.5 mg/animal), a peripheral inhibitor of acetylcholinesterase (AChE), during an immune/inflammatory challenge provoked by intravenous injection of bacterial endotoxin-lipopolysaccharide (LPS; 400 ng/kg)-attenuates the synthesis of proinflammatory cytokines in the ovine preoptic area (POA), the hypothalamic structure playing an essential role in the control of the reproduction process, and in the choroid plexus (CP), a multifunctional organ sited at the interface between the blood and cerebrospinal fluid in the ewe. Neostigmine suppressed (p < 0.05) LPS-stimulated synthesis of cytokines such as interleukin- (IL-) 1ß, IL-6, and tumor necrosis factor (TNF) α in the POA, and this effect was similar to that induced by the treatment with systemic AChE inhibitor-donepezil (2.5 mg/animal). On the other hand, both AChE inhibitors did not influence the gene expression of these cytokines and their corresponding receptors in the CP. It was found that this structure seems to not express the neuronal acetylcholine (ACh) receptor subunit alpha-7, required for anti-inflammatory action of ACh. The mechanism of action involves inhibition of the proinflammatory cytokine synthesis on the periphery as well as inhibition of their de novo synthesis rather in brain microvessels and not in the CP. In conclusion, it is suggested that the AChE inhibitors incapable of reaching brain parenchyma might be used in the treatment of neuroinflammatory processes induced by peripheral inflammation.

Combined administration of anisodamine and neostigmine rescued acute lethal crush syndrome through α7nAChR-dependent JAK2-STAT3 signaling.

Previously we showed that Ani (anisodamine)/Neo (neostigmine) combination produced anti-shock effect via activating α7 nicotinic acetylcholine receptor (α7nAChR). In this study, we aim to investigate the therapeutic effect and underlying mechanisms of Ani/Neo combination in acute lethal crush syndrome (CS). In rat and rabbit CS models, Ani/Neo combination increased the 24 h survival rates, improved hemodynamics and decreased the levels of creatine kinase, MB isoenzyme of creatine kinase, blood urea nitrogen, creatinine, K+ in serum. It also decreased the levels of H2O2, myeloperoxidase (MPO) and nitric oxide (NO) in serum and compressed muscle in rat CS model. In wild-type (WT) mice with CS, Ani/Neo combination increased 24 h survival rate and decreased the levels of H2O2, MPO, NO, TNFα, IL-6 and IL-10 in compressed muscle. These effects were attenuated by α7nAChR knockout (KO). Moreover, Ani/Neo combination prevented the decrease of phosphorylation of Janus kinase 2 (JAK2) and phosphorylation of signal transducer and activator of transcription 3 (STAT3) induced by CS. These effects of Ani/Neo in CS mice were cancelled by methyllycaconitine (α7nAChR antagonist) and α7nAChR KO. Collectively, our results demonstrate that Ani/Neo combination could produce therapeutic effects in CS. The underlying mechanism involves the activation of α7nAChR-dependent JAK2-STAT3 signaling pathway.

Interventions for Treating Heartburn in Pregnancy.

Editor's note: This is a summary of a nursing care-related systematic review from the Cochrane Library.

Interventions for heartburn in pregnancy.

BACKGROUND: Heartburn is one of the most common gastrointestinal symptoms in pregnant women. It can occur in all trimesters of pregnancy. The symptoms of heartburn in pregnancy may be frequent, severe and distressing, but serious complications are rare. Many interventions have been used for the treatment of heartburn in pregnancy. These interventions include advice on diet, lifestyle modification and medications. However, there has been no evidence-based recommendation for the treatment of heartburn in pregnancy. OBJECTIVES: To assess the effects of interventions for relieving heartburn in pregnancy. SEARCH METHODS: We searched the Cochrane Pregnancy and Childbirth Group's Trials Register (30 June 2015), ClinicalTrials.gov (2 March 2015), Asian & Oceanic Congress of Obstetrics & Gynaecology (AOCOG) conference proceedings (20-23 October 2013, Centara Grand & Bangkok Convention Centre, Bangkok, Thailand), and reference lists of retrieved studies. SELECTION CRITERIA: Randomised controlled trials (RCTs) and quasi-RCTS of interventions for heartburn in pregnancy compared with another intervention, or placebo, or no intervention. Cluster-RCTs would have been eligible for inclusion but none were identified. We excluded studies available as abstracts only and those using a cross-over design.Interventions could include advice on diet, lifestyle modification and medications (such as antacids, sucralfate, histamine 2-receptor antagonists, promotility drugs and proton pump inhibitors (PPIs)). DATA COLLECTION AND ANALYSIS: Two review authors independently assessed trials for inclusion and risk of bias, extracted data and checked them for accuracy. MAIN RESULTS: We included nine RCTs involving 725 women. However, five trials did not contribute data. Four trials involving 358 women contributed data. Trials were generally at mixed risk of bias.We only identified data for three comparisons: pharmaceutical treatment versus placebo or no treatment; acupuncture versus no treatment and pharmacological intervention versus advice on dietary and lifestyle changes. Pharmaceutical treatment compared with placebo or no treatmentTwo trials evaluated any pharmaceutical treatment compared with placebo or no treatment. One trial examined a treatment rarely used nowadays (intramuscular prostigmine 0.5 mg versus placebo). One trial evaluated the effect of magnesium and aluminium hydroxide plus simethicone liquid and tablet compared with placebo. For the primary outcome of this review (relief of heartburn), women who received pharmaceutical treatment reported complete heartburn relief more often than women receiving no treatment or placebo (risk ratio (RR) 1.85, 95% confidence interval (CI) 1.36 to 2.50 in two RCTs of 256 women, I(2) = 0%, moderate-quality evidence). Data on partial relief of heartburn were heterogenous and showed no clear difference (average RR 1.35, 95% CI 0.38 to 4.76 in two RCTs of 256 women, very low-quality evidence). In terms of secondary outcomes, there was no clear difference in the rate of side effects between the pharmaceutical treatment group and the placebo/no treatment group (RR 0.63, 95% CI 0.21 to 1.89 in two RCTs of 256 women, very low-quality evidence). Pharmacological intervention versus advice on dietary and lifestyle choicesOne study compared 1 g of sucralfate with advice on dietary and lifestyle choices in treating heartburn. More women in the sucralfate group experienced complete relief of heartburn compared to women who received advice on diet and lifestyle choices (RR 2.41, 95% CI 1.42 to 4.07; participants = 65; studies = one). The only secondary outcome of interest addressed by this trial was side effects. The evidence was not clear on intervention side effects rate between the two groups (RR 1.74, 95% CI 0.07 to 41.21; participants = 66; studies = one). There was only one instance of side effects in the pharmacological group. Acupuncture compared with no treatmentOne trial evaluated acupuncture compared with no treatment but did not report data relating to this review's primary outcome (relief of heartburn). In terms of secondary outcomes, there was no difference in the rate of side effects between women who had acupuncture and women who had no treatment (RR 2.43, 95% CI 0.11 to 55.89 in one RCT of 36 women). With regard to quality of life, women who had acupuncture reported improved ability to sleep (RR 2.80, 95% CI 1.14 to 6.86) and eat (RR 2.40, 95% CI 1.11 to 5.18 in one RCT of 36 women).The following secondary outcomes were not reported upon in any of the trials included in the review: miscarriage, preterm labour, maternal satisfaction, fetal anomalies, intrauterine growth restriction, low birthweight. AUTHORS' CONCLUSIONS: There are no large-scale RCTs to assess heartburn relief in pregnancy. This review of nine small studies (which involved data from only four small studies) indicates that there are limited data suggesting that heartburn in pregnancy could be completely relieved by pharmaceutical treatment. Three outcomes were assessed and assigned a quality rating using the GRADE methods. Evidence from two trials for the outcome of complete relief of heartburn was assessed as of moderate quality. Evidence for the outcomes of partial heartburn relief and side effects was graded to be of very low quality. Downgrading decisions were based in part on the small size of the trials and on heterogenous and imprecise results.There are insufficient data to assess acupuncture versus no treatment and no data to assess other comparisons (miscarriage, preterm labour, maternal satisfaction, fetal anomalies, intrauterine growth restriction, low birthweight).Further RCTs are needed to fully evaluate the effectiveness of interventions for heartburn in pregnancy. Future research should also address other medications such as histamine 2-receptor antagonists, promotility drugs, proton pump inhibitors, and a raft-forming alginate reflux suppressant in treatment of heartburn in pregnancy. More research is needed on acupuncture and other complimentary therapies as treatments for heartburn in pregnancy. Future research should also evaluate any adverse outcomes, maternal satisfaction with treatment and measure pregnant women's quality of life in relation to the intervention.

A combination of neostigmine and anisodamine protects against ischemic stroke by activating α7nAChR.

BACKGROUND: Increasing endogenous acetylcholine by neostigmine decreased the ischemic cerebral injury. The off-target action on muscarinic receptor produced a variety of adverse effects and limited the clinical application on stroke. AIM: We combined neostigmine with anisodamine and investigated the neuroprotection and mechanism. METHODS: Male Sprague-Dawley rats were subjected to middle cerebral artery occlusion. Neuroprotective action of neostigmine in combination with anisodamine at varying ratios was examined to determine the optimal combination as well as ideal therapeutic window. Potential involvement of α7 nicotinic acetylcholine receptor was examined by measuring the infarct size, the expression of proinflammatory cytokines, and the biomarkers of apoptosis in α7 nicotinic acetylcholine receptor knockout mice. A set of in vitro experiments was conducted in RAW264.7 cells to probe into potential molecular mechanisms. RESULTS: The neostigmine/anisodamine combination conferred neuroprotection. The protection was most potent at a ratio of 1:500. At such a ratio, the combination increased the binding of acetylcholine to α7 nicotinic acetylcholine receptor and reduced proinflammatory cytokines. The neuroprotection was evident only in wild-type and not in α7 nicotinic acetylcholine receptor knockout mice. The combination significantly decreased the expression of Bad and Bax, and increased Bcl-2 and Bcl-xl in α7 nicotinic acetylcholine receptor wild-type mice but not in knockout mice. The combination did not affect caspase-8, cleaved caspase-8, or caspase-12. CONCLUSIONS: Current study identified the optimal combination of neostigmine and anisodamine against ischemic stroke, and indicated that the acetylcholine-α7 nicotinic acetylcholine receptor is involved in the protective effects.

[Diagnosis and treatment of acute colonic pseudo-obstruction]. / Diagnostik og behandling af akut colonpseudoobstruktion.

Acute colonic pseudo-obstruction (ACPO), also known as Ogilvie's syndrome, is a clinical condition with acute dilatation of the colon without a provable mechanical cause. Early recognition and treatment of the condition is important in order to improve the outcome. The diagnosis is based on clinical and radiographic findings. Supportive therapy should be the initial management. If no improvement occurs after 24 hours, medical treatment with neostigmine administered i.v. is instituted and repeated if necessary. Colonoscopic decompression is the next step, but if ischaemia or perforation appear surgery should be performed.

Beneficial effect of crotamine in the treatment of myasthenic rats.

INTRODUCTION: Crotamine is a basic, low-molecular-weight peptide that, at low concentrations, improves neurotransmission in isolated neuromuscular preparations by modulating sodium channels. In this study, we compared the effects of crotamine and neostigmine on neuromuscular transmission in myasthenic rats. METHODS: We used a conventional electromyographic technique in in-situ neuromuscular preparations and a 4-week treadmill program. RESULTS: During the in-situ electromyographic recording, neostigmine (17 µg/kg) caused short-term facilitation, whereas crotamine induced progressive and sustained twitch-tension enhancement during 140 min of recording (50 ± 5%, P < 0.05). On the treadmill evaluation, rats showed significant improvement in exercise tolerance, characterized by a decrease in the number of fatigue episodes after 2 weeks of a single-dose treatment with crotamine. CONCLUSIONS: These results indicate that crotamine is more efficient than neostigmine for enhancing muscular performance in myasthenic rats, possibly by improving the safety factor of neuromuscular transmission.

A cohort study on myasthenia gravis patients in China.

Clinical classification and age distribution in myasthenia gravis (MG) cases seem different between Oriental and Caucasian populations, but there have rarely been any clinical studies on MG patients from mainland China. The goal of the current study was to perform a comprehensive survey of myasthenia gravis in a hospital in China, establishing contemporary cohort data and clinical features. 1,108 unselected patients with MG attending the 309th Hospital of PLA, Beijing, China were studied during a 36-month period from July 2008 to June 2011. The sex ratio was 1:1 (F:M). 62.5 % of patients presented as adolescents and adults. Ocular MG cases accounted for 65.6 % childhood MG patients. A positive response was observed in 96.8 % of the patients for neostigmine tests, whereas a positive decremental response to low frequency repetitive nerve stimulation (RNS) was observed in 77.4 % of the patients. The highest stimulating positive rate was 65.3 % in stimulated facial nerve. Thymoma was significantly increased in those patients with severe MG, especially in the cohort involving the respiratory muscles (p < 0.001). The study revealed higher frequency of ocular and childhood MG compared to other studies in USA and European countries, which can be a result of optimum case ascertainment, increased disease duration, or application of complex diagnostic tests. The relative increase in the prevalence of ocular myasthenia can be attributed to the impact of an aging population.

Combined administration of anisodamine and neostigmine produces anti-shock effects: involvement of α7 nicotinic acetylcholine receptors.

AIM: To evaluate the anti-effects of anisodamine and neostigmine in animal models of endotoxic and hemorrhagic shock. METHODS: Kunming mice were injected with lipopolysaccharide (LPS 30 mg/kg, ip) to induce endotoxic shock. Anisodamine (12.5, 25, and 50 mg/kg, ip) and neostigmine (12.5, 25, and 50 µg/kg, ip) were administered immediately after LPS injection. Survival rate was monitored, and the serum levels of TNF-α and IL-1ß were analyzed using ELISA assays. The effects of anisodamine and neostigmine were also examined in α7 nicotinic acetylcholine receptor (α7 nAChR) knockout mice with endotoxic shock and in Beagle dogs with hemorrhagic shock. RESULTS: In mice with experimental endotoxemia, combined administration of anisodamine and neostigmine significantly increased the survival rate and decreased the serum levels of inflammatory cytokines, as compared to those produced by either drug alone. The anti-shock effect of combined anisodamine and neostigmine was abolished in α7 nAChR knockout mice. On the other hand, intravenous injection of the combined anisodamine and neostigmine, or the selective α7 nAChR agonist PNU282987 exerted similar anti-shock effects in dogs with hemorrhagic shock. CONCLUSION: The results demonstrate that combined administration of anisodamine and neostigmine produces significant anti-shock effects, which involves activation of α7 nAChRs.

Modern neuraxial labor analgesia: options for initiation, maintenance and drug selection

En la presente revisión se destaca el estado actual de laanalgesia neuraxial. Dado que la analgesia neuraxial continuasiendo la más utilizada durante el parto, hemos realizadouna revisión de la literatura más reciente sobre estamateria. Las técnicas de analgesia neuraxial, los tipos deadministración, los fármacos, los adyuvantes y los efectosadversos se han investigado desde las referencias bibliográficas.La mayor parte de los autores se muestran de acuerdoen que la analgesia neuraxial central es la mejor manerade manejar el dolor durante el parto. Cuando la analgesianeuraxial se administra a la parturienta en el parto, diferentesopciones de manejo deben ser llevadas a cabo por elanestesista: cuándo iniciaremos la analgesia, durante cuántotiempo deberemos mantenerla, qué anestésico local usaremospara la analgesia neuraxial y qué fármacos adyuvantescombinaremos. El presente manuscrito intenta revisar laliteratura para responder a estas cuestiones(AU)

In the present review we outline the state-of-the-art ofneuraxial analgesia. As neuraxial analgesia remains thegold standar of analgesia during labor, we review themost recent literature on this topic. The neuraxial analgesiatechniques, types of administration, drugs, adjuvants,and adverse effects are investigated from the references.Most authors would agree that central neuraxialanalgesia is the best form to manage labor pain. Whenneuraxial analgesia is administered to the parturient inlabor, different management choices must be made bythe anesthetist: how will we initiate analgesia, how willanalgesia be maintained, which local anesthetic will weuse for neuraxial analgesia and which adjuvant drugswill we combine? The present manuscript tries to reviewthe literature to answer these questions(AU)

Colonic pseudo-obstruction.

Colonic pseudo-obstruction is often confused with mechanical intestinal obstruction. It occurs when there is an autonomic imbalance resulting in sympathetic over-activity affecting some part of the colon. The patient is often elderly with numerous comorbidities. Once mechanical obstruction is excluded by contrast enema, the patient should be treated conservatively with nasogastric and flatus tubes for at least 48 hours, and precipitating factors should be treated. When pseudo-obstruction does not settle with waitful watching, prokinetic agents and/or colonoscopic decompression can be tried. When there is a risk of impending perforation of the caecum from massive colonic dilatation and colonic ischaemia, it should be dealt with by caecostomy or hemicolectomy. In spite of available medical and surgical interventions, the outcome remains poor.

A new approach to the cure of the Ogilvie's syndrome.

The Authors describe a their own observation of 25 cases of acute colonic pseudo obstruction, better known as "Ogilvie Syndrome" with the objective to demonstrate that an early recognition and prompt appropriate therapy, better if conservative, can reduce the morbidity and the mortality of the Syndrome. The surgical therapy is reserved only to that cases in which the risk of perforation of the cecum represent an absolute indication to intervention.

[Moot questions and rarely employed means of treatment for severe forms of diphtheria in adults]. / O nekotorykh diskussionnykh voprosakh i redko primeniaemykh metodakh lecheniia tiazheloi formi difterii i ee oslozhnenii u vzroslykh.

The authors of the article consider the issue of employment of some treatment options for the grave forms of diphtheria and complications thereof in adult subjects to be a matter of debate and they report their experience gained with the use of rarely employed but efficient means of remediation. In diphtherial myocarditis concurrent with acute renal failure with a critical uncorrectable decline in myocardial contractility in spite of a progressive necrosis of the renal parenchyma due to an inadequate perfusion and toxic nephrosis an adrenomimetic drug (depamine) is to be prescribed. A ban on administration of glycosides is not to be regarded as a dogma. The question of their prescription needs to be decided on an individual basis with due regard to the duration of the illness, degree of cardiac decompensation, and whether it is conduction/contractility function disorders that prevail. Severe forms of diphtheria, including that complicated by myocarditis, especially concurrent with alcohol intoxication have been shown to be alleviated by intravenous administration of 0.015% sodium hypochlorite solution. In diphtheric polyneuritis it was anticholinesterase agents (neostigmine methylsulfate up to 6 mg daily) in maximum permissible doses that the authors employed in critical cases together with hyperbaric oxygenation and, as a means to improve metabolism,--lecithin and amniocen, a biological stimulant from human placenta.

Retrospective study of neostigmine for the treatment of acute colonic pseudo-obstruction.

Acute colonic pseudo-obstruction (ACPO) typically develops postoperatively or after severe illness. Studies suggest that pharmacologic manipulation with intravenous (i.v.) neostigmine (NSM) may be an effective and less invasive treatment modality for ACPO with minimal side effects. The purpose of this study was to retrospectively assess the efficacy and incidence of complications of an i.v. NSM bolus in patients with ACPO. Eight patients with ten episodes of ACPO were treated with a bolus dose of NSM. Rapid and effective decompression of the colon was achieved in six episodes after a single dose of NSM at a mean of 22.8 +/- 13.5 minutes. In three episodes decompression occurred after a second dose of NSM at a mean of 44.7 +/- 37.7 minutes. One patient failed NSM treatment but responded to a Cystografin enema. One patient experienced significant bradycardia. NSM is a simple, safe, and effective treatment for ACPO and based on result comparison of this study and previous studies both bolus and slow infusion dosing practices of NSM are effective. The NSM bolus dosing side effect profile has been shown to include significant bradycardia, whereas when NSM was infused over one hour significant bradycardic episodes requiring treatment have not been encountered. We propose that a prospective study evaluating NSM dosing as an i.v. bolus versus an i.v. infusion would be useful in determining whether NSM infusion can be proven safer than bolus dosing for the treatment of ACPO.

A female with central anticholinergic syndrome responsive to neostigmine.

Central anticholinergic syndrome is a rarely observed condition in children. The occurrence of this syndrome after ingestion of Solanum pseudocapsicum is infrequent because findings tend to be milder and localized to the gastrointestinal system, without central nervous system involvement. Most patients do not present with diagnostic problems because their relatives can usually report any ingestion of poisonous agents; however, when drug poisoning or plant ingestion is uncertain, a differential diagnosis with encephalitis must be considered. Physostigmine salicylate is the specific antidote because it crosses the blood-brain barrier because of its tertiary ammonium group. Neostigmine methylsulfate has a quaternary ammonium group, which prevents its penetration through the blood-brain barrier; hence its primary influence is believed to be due to its action on the peripheral nervous system. We describe a female with central anticholinergic syndrome caused by ingestion of Solanum pseudocapsicum. A slow intravenous infusion of neostigmine methylsulfate (0.03 mg/kg) immediately resolved the clinical picture. To our knowledge, this case is the first reported of central anticholinergic syndrome occurring after ingestion of Solanum pseudocapsicum in a child and the first report of a complete and rapid remission after intravenous neostigmine methylsulfate administration.

Tactile evaluation of the response to double burst stimulation decreases, but does not eliminate, the problem of postoperative residual paralysis.

BACKGROUND: Routine perioperative monitoring with accelero-myography might prevent residual block, whereas routine tactile evaluation of the response to train-of-four (TOF) nerve stimulation does not. The purpose of this prospective, randomised and blinded study was to evaluate the effect of manual evaluation of the response to double burst stimulation (DBS3.3) upon the incidence of residual block. METHODS: Sixty adult patients scheduled for elective abdominal surgery were included in the study. Pancuronium 0.08 to 0.1 mg kg-1 was given for relaxation and tracheal intubation. For maintenance of neuromuscular block, pancuronium 1-2 mg was administered. The patients were randomly allocated into two groups. In group DBS (double burst stimulation) the degree of block during anaesthesia was assessed by manual evaluation of the response to TOF nerve stimulation. During reversal, when no fade was detectable in the TOF response, the stimulation pattern was changed to DBS3.3. The trachea was extubated when the anaesthetist judged the neuromuscular function to have recovered adequately and no fade in the DBS3.3 response could be felt. In group CC (clinical criteria) patients were managed without the use of a nerve stimulator, and the level of neuromuscular block and reversal were evaluated solely on the basis of clinical criteria. In both groups, the TOF ratio was measured by mechanomyography immediately after tracheal extubation. Also, the ability to sustain head lift for 5 s, to protrude the tongue, to open the eyes, and to lift one arm to the opposite shoulder were tested. RESULTS: The TOF ratio, as measured immediately after tracheal extubation, was significantly lower in group CC than in group DBS (means: 0.68 and 0.78, respectively), and the incidence of residual neuromuscular block defined as a TOF ratio < 0.7 was significantly higher in group CC than in group DBS (57 and 24%, respectively). The time from the first TOF measurement until the TOF ratio reached 0.8 was significantly longer in group CC than in group DBs (means: 11.5 and 6.2 min, respectively). No significant differences between the two groups of patients were found in duration of anaesthesia, in times from end of surgery to injection of neostigmine, tracheal extubation or TOF ratio 0.8, in dose of pancuronium, or in any other postoperative variable. CONCLUSION: Routine perioperative manual evaluation of the responses to TOF and DBS3.3 decreased the incidence and the degree of residual block following the use of pancuronium. It did not, however, exclude clinically significant residual paralysis, nor did it influence the amount of pancuronium used during the operation, the duration of anaesthesia or the time from end of surgery to tracheal extubation or to sufficient recovery of neuromuscular function (TOF = 0.8).