Anesthetic pretreatment confers thermotolerance on Saccharomyces cerevisiae yeast.

Saccharomyces cerevisiae yeast, when pretreated with elevated temperatures, undergo adaptive changes that promote survival after an otherwise lethal heat stress. The heat shock response, a cellular stress response variant, mediates these adaptive changes. Ethanol, a low-potency anesthetic, promotes thermotolerance possibly through heat shock response activation. Therefore, we hypothesized other anesthetic compounds, like ethanol, may invoke the heat shock response to promote thermotolerance. To test this hypothesis, we pretreated yeast with a series of non-volatile anesthetic and anesthetic-related compounds and quantified survival following lethal heat shock (52 °C for 5 min). Most compounds invoked thermoprotection and promoted survival with a potency proportional to hydrophobicity: tribromoethanol (5.6 mM, peak survival response), trichloroethanol (17.8 mM), dichloroethanol (100 mM), monochloroethanol (316 mM), trifluoroethanol (177.8 mM), ethanol (1 M), isopropanol (1 M), propofol (316 µM), and carbon tetrabromide (32 µM). Thermoprotection conferred by pretreatment with elevated temperatures was "left shifted" by anesthetic co-treatment from (in °C) 35.3 ± 0.1 to 32.2 ± 0.1 with trifluoroethanol (177.8 mM), to 31.2 ± 0.1 with trichloroethanol (17.8 mM), and to 29.1 ± 0.3 with tribromoethanol (5.6 mM). Yeast in postdiauxic shift growth phase, relative to mid-log, responded with greater heat shock survival; and media supplementation with tryptophan and leucine blocked thermoprotection, perhaps by reversing the amino acid starvation response. Our results suggest S. cerevisase may serve as a model organism for understanding anesthetic toxicity and anesthetic preconditioning, a process by which anesthetics promote tissue survival after hypoxic insult.

Parenteral amino acids v. dextrose infusion: an anabolic strategy to minimise the catabolic response to surgery while maintaining normoglycaemia in diabetes mellitus type 2 patients.

Loss of body protein and hyperglycaemia represent typical features of the stress response to surgery and anaesthesia. This appears to be particularly pronounced in patients with diabetes mellitus type 2. The aim of the present study was to highlight the greater benefit of amino acids (AA) as represented by positive protein balance and maintenance of blood glucose homoeostasis compared with dextrose (DEX) in diabetic patients after colorectal surgery. A total of thirteen patients underwent a 5 h stable isotope infusion study (2 h fasted, 3 h fed with an infusion of AA (n 6) or DEX (n 7)) on the second post-operative day. Glucose and protein kinetics were assessed by using the stable isotopes l-[1-¹³C]leucine and [6,6-²H2]glucose. The transition from fasted to fed state decreased endogenous glucose production (P < 0·001) in both groups, with a more profound effect in the DEX group (P = 0·031). In contrast, total glucose production was increased by the provision of DEX while being lowered by AA (P = 0·021). Feeding decreased protein oxidation (P = 0·009) and protein synthesis in the AA group, whereas DEX infusion did not affect oxidation and even decreased protein synthesis. Therefore, only AA shifted protein balance to a positive value, while patients in the DEX group remained in a catabolic state (P < 0·001). Parenteral nutritional support with AA rather than with DEX is an effective strategy to achieve a positive protein balance while maintaining normoglycaemia in diabetic patients after colorectal surgery.

Postoperative patient complaints: a prospective interview study of 12,276 patients.

STUDY OBJECTIVE: To evaluate the incidence of perioperative minor adverse events and to analyze patient satisfaction based on potential explanatory variables. DESIGN: Structured, face-to-face interview of 25% of all patients undergoing surgery during the period from January 2003 through June 2006. SETTING: Academic university medical center. PATIENTS: 12,276 patients (5,793 men and 6,483 women) from all surgical disciplines: 7,440 patients had general anesthesia, 4,236 patients had regional anesthesia, and 600 patients had a combined general-regional anesthetic technique. MEASUREMENTS: Occurrence of perioperative minor adverse events was assessed during the interview. Patient satisfaction was measured with a 4-point Likert scale. MAIN RESULTS: 3,652 (30%) patients reported at least one perioperative complaint and 737 (6%) patients reported multiple minor adverse events. Overall, a total of 4,475 minor adverse events were reported. Leading adverse events included postoperative nausea and vomiting (1,705 complaints), sore throat (1,228 complaints), and hoarseness (802 complaints). Patient satisfaction with anesthetic care was generally high (97% satisfied or highly satisfied). Patients were significantly more satisfied following regional than general anesthesia (P < 0.001). Patient dissatisfaction was also associated with the occurrence of at least one minor adverse event (P < 0.001) or with increasing ASA physical status (P < 0.001). CONCLUSION: Minor events occur with a surprisingly high incidence and are significantly associated with patient dissatisfaction. Regional anesthesia is associated with fewer patient complaints and significantly higher postoperative patient satisfaction.

B-type natriuretic peptide in patients undergoing orthopaedic surgery: a prospective cohort study.

BACKGROUND AND OBJECTIVE: Postoperative cardiac complications pose a substantial risk to patients undergoing orthopaedic surgery. METHODS: B-type natriuretic peptide (BNP) was determined preoperatively in 270 patients undergoing scheduled orthopaedic surgery. The accuracy of BNP to predict the occurrence of in-hospital cardiac events was evaluated as the primary endpoint. Cardiac events at 1 year of follow-up were considered secondary endpoints. RESULTS: Preoperative BNP levels were significantly higher in the four patients experiencing in-hospital cardiac events than in patients without events [median 306 pg ml(-1) (range 123-3958) vs. 35 pg ml(-1) (range 14-2074), P = 0.01]. In a receiver operating characteristic analysis for the prediction of in-hospital cardiac events, the area under the receiver operating characteristic curve for BNP was 0.86 (95% confidence interval 0.74-0.99). The optimal predictive accuracy was achieved with a BNP threshold of 174 pg ml(-1). Importantly, the combination of BNP and the American Society of Anesthesiologists score further improved this accuracy. Additionally, BNP retained a high predictive accuracy in the subgroup of patients with known cardiac diseases [area under the receiver operating characteristic curve 0.85 (95% confidence interval from 0.65 to <1)]. The area under the receiver operating characteristic curve for the prediction of long-term cardiac events by BNP was 0.71 (95% confidence interval 0.57-0.84). CONCLUSION: In patients undergoing orthopaedic surgery, preoperative BNP levels can predict short-term and long-term postoperative cardiac events. Despite the paucity of endpoint events observed in this study, our results are in agreement with all prior investigations. BNP used in addition to an American College of Cardiology/American Heart Association guideline-based risk assessment might, therefore, be a useful tool in the preoperative evaluation of patients undergoing orthopaedic surgery.

[The preoperative anaesthetic visit]. / Das präoperative anästhesiologische Patientengespräch.

Anaesthetists often visit their patients in exceptional situations characterised by preoperative anxiety or distress. Therefore, even brief contact with the patient can be considered intense and meaningful. The initial preoperative anaesthetic visit is the beginning of the relationship between patient and anaesthetist, and should help to explain the planned anaesthetic technique. Preoperative anaesthetic visits are intense and last for 20 minutes on average. They should assert a professional approach to the patient's emotions, particularly to preoperative anxiety, and a structured and clear collection of information including the past history of the patient. These visits should also provide information about the anaesthesia itself and instructions for the patient with respect to the perioperative period. Communication about the side effects and risks of anaesthetic techniques, and the discussion of potential alternatives are mandatory. Worldwide, courts of law increasingly require a documented discussion between the anaesthetist and patient based on risk-benefit evidence. Today, there is in general a shift away from decisions made solely by physicians, reflecting an increased respect for the autonomy of the patient towards a model of shared decision-making and informed choice. Ideally, the preoperative visit follows the four key habits of highly effective clinicians, i.e., to rapidly establish a rapport with the patient and provide an agenda for the visit, to explore the patient's perspectives and expectations, to demonstrate empathy, and to focus on the end of the visit with providing information and including the patient in the decision-making process. Visits are then concluded upon obtaining informed consent from the patient.

Anaesthetic mechanisms: update on the challenge of unravelling the mystery of anaesthesia.

General anaesthesia is administered each day to thousands of patients worldwide. Although more than 160 years have passed since the first successful public demonstration of anaesthesia, a detailed understanding of the anaesthetic mechanism of action of these drugs is still lacking. An important early observation was the Meyer-Overton correlation, which associated the potency of an anaesthetic with its lipid solubility. This work focuses attention on the lipid membrane as a likely location for anaesthetic action. With the advent of cellular electrophysiology and molecular biology techniques, tools to dissect the components of the lipid membrane have led, in recent years, to the widespread acceptance of proteins, namely receptors and ion channels, as more likely targets for the anaesthetic effect. Yet these accumulated data have not produced a comprehensive explanation for how these drugs produce central nervous system depression. In this review, we follow the story of anaesthesia mechanisms research from its historical roots to the intensely neurophysiological research regarding it today. We will also describe recent findings that identify specific neuroanatomical locations mediating the actions of some anaesthetic agents.

Active research fields in anesthesia: a document co-citation analysis of the anesthetic literature.

BACKGROUND: The expansion of science has resulted in an increased information flow and in an exponentially growing number of connections between knowledge in different research fields. In this study, we used methods of scientometric analysis to obtain a conceptual network that forms the structure of active scientific research fields in anesthesia. METHODS: We extracted from the Web of Science (Institute for Scientific Information) all original articles (n = 3275) including their references (n = 79,972) that appeared in 2003 in all 23 journals listed in the Institute for Scientific Information Journal Citation Reports under the subject heading "Anesthesiology." After identification of highly cited references (> or = 5), pairs of co-cited references were created and grouped into uniformly structured clusters of documents using a single linkage and variable level clustering method. In addition, for each such cluster of documents, we identified corresponding front papers published in 2003, each of which co-cited at least two documents of the cluster core. Active anesthetic research fields were then named by examining the titles of the documents in both the established clusters and in their corresponding front papers. These research fields were sorted according to the proportion of recent documents in their cluster core (immediacy index) and were further analyzed. RESULTS: Forty-six current anesthetic research fields were identified. The research field named "ProSeal laryngeal mask airway" showed the highest immediacy index (100%) whereas the research fields "Experimental models of neuropathic pain" and "Volatile anesthetic-induced cardioprotection" exhibited the highest level of co-citation strength (level 9). The research field with the largest cluster core, containing 12 homogeneous papers, was "Postoperative nausea and vomiting." The journal Anesthesia & Analgesia published most front papers while Anesthesiology published most of the fundamental documents used as references in the front papers. CONCLUSIONS: Using co-citation analysis, we identified distinct homogenous clusters of highly cited documents representing 46 active current anesthetic research fields and determined multiple nets of knowledge among them.

Patient satisfaction with continued versus divided anesthetic care.

STUDY OBJECTIVE: To evaluate patient acceptability of continued versus divided anesthetic care. DESIGN: Patient satisfaction ratings with continuous and divided anesthetic care were assessed by patient questionnaire. In addition, the effect of training anesthesia personnel in communication regarding divided anesthesia care was examined. SETTING: University medical center. PATIENTS: 654 consecutive patients scheduled for elective surgery. MEASUREMENTS AND MAIN RESULTS: Overall postoperative patient satisfaction was high and not different between patients experiencing continued or divided anesthetic care (P=0.97). Asking patients before their operations about the importance of continued anesthetic care resulted in a highly significant difference between the two groups. In the continued anesthetic care model, patients felt it more important to experience continued care. In contrast, patients who were told that another anesthesiologist would take care of them rated the same question with a lower importance (P<0.001). CONCLUSION: Before their operations, more than half of the patients felt it very important that they were visited and anesthetized by the same physician. Nevertheless, postoperative patient satisfaction was equally high regardless of whether they were anesthetized by the same physician who had visited them preoperatively.

Species-specific differences in response to anesthetics and other modulators by the K2P channel TRESK.

UNLABELLED: TRESK (TWIK-related spinal cord K+ channel) is the most recently characterized member of the tandem-pore domain potassium channel (K2P) family. Human TRESK is potently activated by halothane, isoflurane, sevoflurane, and desflurane, making it the most sensitive volatile anesthetic-activated K2P channel yet described. Herein, we compare the anesthetic sensitivity and pharmacologic modulation of rodent versions of TRESK to their human orthologue. Currents passed by mouse and rat TRESK were enhanced by isoflurane at clinical concentrations but with significantly lower efficacy than human TRESK. Unlike human TRESK, the rodent TRESKs are strongly inhibited by acidic extracellular pH in the physiologic range. Zinc inhibited currents passed by both rodent TRESK in the low micromolar range but was without effect on human TRESK. Enantiomers of isoflurane that have stereoselective anesthetic potency in vivo produced stereospecific enhancement of the rodent TRESKs in vitro. Amide local anesthetics inhibited the rodent TRESKs at almost 10-fold smaller concentrations than that which inhibit human TRESK. These results identified interspecies differences and similarities in the pharmacology of TRESK. Further characterization of TRESK expression patterns is needed to understand their role in anesthetic mechanisms. IMPLICATIONS: Mouse and rat TRESK (TWIK-related spinal cord K+ channel) have different pharmacologic responses compared with human TRESK. In particular, we found stereospecific differences in response to isoflurane by the rodent TRESKs but not by human TRESK. TRESK may be a target site for the mechanism of action of volatile anesthetics.

Antiemetics of the 5-hydroxytryptamine 3A antagonist class inhibit muscle nicotinic acetylcholine receptors.

Antagonists of the serotonergic 5-hydroxytryptamine 3A receptor (5-HT(3A)R) and muscle nicotinic acetylcholine receptors (nAChR) are widely used in anesthesia practice. Both 5-HT(3A)R and nAChR are ligand-gated ion channels with known pharmacological overlap between some of their agonists and antagonists. We studied the actions of clinically used 5-HT(3A)R antagonist antiemetics and nondepolarizing muscle blockers on ionic currents elicited by the activation of mammalian 5-HT(3A)R and muscle nAChR, expressed in Xenopus laevis oocytes. Currents were recorded using a whole-cell two-electrode voltage clamp technique. Dolasetron, ondansetron, and granisetron reversibly inhibited 5-HT(3A)R function at nanomolar concentrations with 50% inhibitory concentrations (IC(50)) of 11.8, 6.4, and 0.2 nM; the rank order of inhibition correlated well with their clinical antiemetic potencies. The principal metabolite of dolasetron, hydrodolasetron, was 40 times more potent than the parent compound on 5-HT(3A)R (IC(50) = 0.29 nM). The potency of the nondepolarizing muscle blocker d-tubocurarine in blocking 5-HT(3A)R was similar to that of the antiemetics and significantly more than vecuronium and rapacuronium (IC(50) = 11.4 nM, 18.9 microM, 60.5 microM). Conversely, ondansetron, dolasetron, and granisetron also reversibly inhibited nAChR currents in a dose-dependent manner with IC(50)s of 14.2, 7.8, and 4.4 microM for the adult nAChR and 16.0, 18.6, and 13.9 microM for the embryonic nAChR. Again, hydrodolasetron showed significantly (10 times) more inhibitory potency on the adult nAChR than the parent compound dolasetron. These results indicate that drugs that target specific ligand-gated ion channels may also affect other ion channel types.

Two-pore domain potassium channels: new sites of local anesthetic action and toxicity.

Potassium (K+) channels form the largest family of ion channels with more than 70 such genes identified in the human genome. They are organized in 3 superfamilies according to their predicted membrane topology: (1) subunits with 6 membrane-spanning segments and 1-pore domain, (2) subunits with 2 membrane-spanning segments and 1-pore domain, and (3) subunits with 4 membrane-spanning segments and 2-pore domains arrayed in a tandem position. The last family has most recently been identified and comprises the so-called 2-pore domain potassium (K2P) channels, believed responsible for background or leak K+ currents. Despite their recent discovery, interest in them is growing rapidly with more than 270 references in the literature reported (www.ipmc.cnrs.fr/~duprat/2p/ref2p.htm#2P, accessed October 30, 2004). K2P channels are widely expressed in the central nervous system and are involved in the control of the resting membrane potential and the firing pattern of excitable cells. This article will therefore review recent findings on actions of local anesthetics with respect to 2P channels. It begins with an overview of the role of background K+ channels in neuronal excitability and nerve conduction and is followed by a description of the K2P channel family including experimental evidence for the contribution of K2P channels to the mechanism of action and toxicity of local anesthetics.

Sevoflurane decreases bispectral index values more than does halothane at equal MAC multiples.

At the minimum alveolar concentration (MAC) of inhaled anesthetics, 50% of subjects move in response to noxious stimulation. Similarly, at MAC-awake, 50% of subjects respond appropriately to command. The bispectral index (BIS) nominally measures the effect of anesthetics on wakefulness or consciousness. We postulated that the use of halothane with a larger MAC-awake/MAC ratio than sevoflurane would produce higher BIS values at comparable levels of MAC. We studied 33 unpremedicated patients anesthetized by inhalation, 18 with sevoflurane and 15 with halothane. We measured BIS before and during anesthesia at 1 MAC, both before and after tracheal intubation facilitated by fentanyl and rocuronium and then at 1.5 MAC. BIS measurements were made after meeting steady-state conditions. No surgery was performed during this study. BIS values in awake patients did not differ between the sevoflurane and halothane groups (96 +/- 2 and 96 +/- 2, mean +/- sd, respectively). At 1 MAC without and with neuromuscular blockade and at 1.5 MAC, BIS values for patients anesthetized with halothane (54 +/- 7, 56 +/- 7, and 49 +/- 7, respectively) exceeded those for patients anesthetized with sevoflurane (34 +/- 6, 34 +/- 6, and 29 +/- 5, respectively) (P < 0.0001). This finding adds to other evidence indicating that BIS is drug specific.

Small-dose intrathecal clonidine and isobaric bupivacaine for orthopedic surgery: a dose-response study.

We examined the dose-response relationship of intrathecal clonidine at small doses (

Citation classics in critical care medicine.

OBJECTIVE: The number of citations an article receives after its publication reflects its impact on the scientific community. Our purpose was to identify and examine the characteristics of the most frequently cited articles in the field of critical care medicine. DESIGN: The 74 top-cited articles in critical care journals were identified by a computer search using the database of the Science Citation Index Expanded (SCI-EXPANDED, 1945 to present) and the Web of SCIENCE. The 45 top-cited critical care articles in all other biomedical journals were identified using the database SciSearch (1974 to present) with the key word "Critical Care". RESULTS: The most cited articles received 3402 and 2860 citations, respectively. The citation classics in critical care journals were published between 1968 and 1999 in six high-impact journals, led by Critical Care Medicine (37 articles), followed by the Journal of Trauma (21), and American Journal of Respiratory and Critical Care Medicine (9). Seventy articles were original publications, two were reviews or guidelines, and two were editorials. The top 45 classic articles in non-critical care journals were published in 13 different journals, led by the New England Journal of Medicine (11 articles), followed by JAMA and Lancet (6 articles each). The United States of America contributed most of the classic articles. Pathophysiology of the lung, sepsis and scoring systems were the primary focus of classic publications. CONCLUSIONS: Our analysis gives a historical perspective on the scientific progress of critical care medicine and allows for recognition of important advances in this specialty.

Citation classics in anesthetic journals.

UNLABELLED: The number of citations an article receives after its publication reflects its recognition in the scientific community. In the present study, therefore, we identified and examined the characteristics of the top 100 most frequently cited articles published in anesthetic journals. These articles were identified using the database of the Science Citation Index Expanded (SCI-EXPANDED, 1945 to present) and the Web of SCIENCE(R). The most-cited article received 707 citations and the least cited article received 197 citations, with a mean of 283 citations per article. These citation classics were published between 1954 and 1997 in 5 high-impact anesthetic journals, led by Anesthesiology (73 articles) followed by Anesthesia & Analgesia (10), British Journal of Anesthesia (10), Anesthesia (6), and Acta Anaesthesiologica Scandinavica (2). Seventy-eight articles were original publications, 22 were review articles, and one was an editorial. They originated from nine countries, with the United States contributing 70 articles. Within the United States, California leads the list of citation classics with 25 articles. Twenty-nine persons authored two or more of the top-cited articles. The main topics covered by the top-cited articles are pharmacology, volatile anesthetics, circulation, regional anesthesia, and lung physiology. This analysis of citation rates allows for the recognition of seminal advances in anesthesia and gives a historic perspective on the scientific progress of this specialty. IMPLICATIONS: We performed a citation analysis to identify important contributions and contributors to the anesthetic literature. These classic articles have influenced many people and have brought to our attention the many important advances in anesthesia made during the last 50 yr.

Genomic structure, cochlear expression, and mutation screening of KCNK6, a candidate gene for DFNA4.

KCNK6 encodes a tandem pore domain potassium channel, TWIK-2, that maps to chromosome 19. Both STS and linkage maps established KCNK6 as a positional candidate gene for DFNA4, a form of autosomal dominant nonsyndromic hereditary hearing loss. Identification and characterization of Kcnk6 expression within the mammalian cochlea established the gene as a functional candidate for DFNA4. Identification of Twik-2 expression in the mouse cochlea was initially established via RT-PCR assay of cochlear RNA. Subsequent immunoblot analysis of cochlear homogenate yielded a distinct 35-kDa band corresponding to the calculated molecular weight of the mouse Twik-2. Immunohistochemical studies localized Twik-2 expression in the cochlea predominantly within the stria vascularis. This vascular tissue borders the cochlear duct and is a critical regulator of potassium concentration in the endolymph. Genomic structure of TWIK-2 was subsequently determined and shown to consist of three coding exons with splice acceptor and donor sites in accordance with the consensus GT-AG rule. Two separate DFNA4 families were screened for KCNK6 sequence alterations. No mutations were found, thus excluding TWIK-2 as the DFNA4 candidate disease gene. Nevertheless, expression of Twik-2 within the stria vascularis suggests a potential role for this protein as one of the terminal components of the potassium ion-recycling pathway that contributes toward its reabsorption into the endolymph.

Amide local anesthetics potently inhibit the human tandem pore domain background K+ channel TASK-2 (KCNK5).

Blockade of voltage-gated sodium (Na+) channels by local anesthetics represents the main mechanism for inhibition of impulse propagation. Local anesthetic-induced potassium (K+) channel inhibition is also known to influence transmission of sensory impulses and to potentiate inhibition. K+ channels involved in this mechanism may belong to the emerging family of background tandem pore domain K+ channels (2P K+ channels). To determine more precisely the effects of local anesthetics on members of this ion channel family, we heterologously expressed the 2P K+ channels TASK-2 (KCNK5), TASK-1 (KCNK3), and chimeric TASK-1/TASK-2 channels in oocytes of Xenopus laevis. TASK-2 cDNA-transfected HEK 293 cells were used for single-channel recordings. Local anesthetic inhibition of TASK-2 was dose-dependent, agent-specific, and stereoselective. The IC50 values for R-(+)-bupivacaine and S-(-)-bupivacaine were 17 and 43 micro M and for R-(+)-ropivacaine and S-(-)-ropivacaine, 85 and 236 micro M. Lidocaine (1 mM) inhibited TASK-2 currents by 55 +/- 4%, whereas its quaternary positively charged analog N-ethyl lidocaine (QX314) had no effect. Bupivacaine (100 micro M) decreased channel open probability from 20.8 +/- 1.6% to 5.6 +/- 2.2%. Local anesthetics [300 micro M R-(+)-bupivacaine] caused significantly greater depolarization of the resting membrane potential of TASK-2-expressing oocytes compared with water-injected control oocytes (15.8 +/- 2.5 mV versus 0.1 +/- 0.05 mV; p < 0.001). Chimeric TASK-1/TASK-2 2P K+ channel subunits that retained pH sensitivity demonstrated that the carboxy domain of TASK-2 mediates the greater local anesthetic sensitivity of TASK-2. These results show that clinically achievable concentrations of local anesthetics inhibit background K+ channel function and may thereby enhance conduction blockade.

Characterization of the interactions between volatile anesthetics and neuromuscular blockers at the muscle nicotinic acetylcholine receptor.

UNLABELLED: Volatile anesthetics enhance the neuromuscular blockade produced by nondepolarizing muscle relaxants (NDMRs). The neuromuscular junction is a postulated site of this interaction. We tested the hypothesis that volatile anesthetic enhancement of muscle relaxation is the result of combined drug effects on the nicotinic acetylcholine receptor. The adult mouse muscle nicotinic acetylcholine receptor (alpha(2), beta, delta, epsilon) was heterologously expressed in Xenopus laevis oocytes. Concentration-effect curves for the inhibition of acetylcholine-induced currents were established for vecuronium, d-tubocurarine, isoflurane, and sevoflurane. Subsequently, inhibitory effects of NDMRs were studied in the presence of the volatile anesthetics at a concentration equivalent to half the concentration producing a 50% inhibition alone. All individually tested compounds produced rapid and readily reversible concentration-dependent inhibition. The calculated 50% inhibitory concentration values were 9.9 nM (95% confidence interval [CI], 8.4-11.4 nM), 43.4 nM (95% CI, 33.6-53.3 nM), 897 microM (95% CI, 699-1150 microM), and 818 microM (95% CI, 685-1001 microM) for vecuronium, d-tubocurarine, isoflurane, and sevoflurane, respectively. Coapplication of either isoflurane or sevoflurane significantly enhanced the inhibitory effects of vecuronium and d-tubocurarine, especially so at small concentrations of NDMRs. Volatile anesthetics increase the potency of NDMRs, possibly by enhancing antagonist affinity at the receptor site. This effect may contribute to the clinically observable enhancement of neuromuscular blockade by volatile anesthetics. IMPLICATIONS: Isoflurane and sevoflurane enhance the receptor blocking effects of nondepolarizing muscle relaxants on nicotinic acetylcholine receptors.