Syphilis-related rapidly progressive glomerulonephritis: a case presentation.

BACKGROUND: Syphilis is a multisystemic infection that causes a wide variety of symptoms and thus has been dubbed one of the great medical mimickers. Due to recent global re-emergence of syphilis, it has become important to recognize its various presentations. Relative to the kidney, syphilitic infections generally present themselves with nephrotic range proteinuria, and are most often associated with pathological features of a membranous glomerulonephritis with subepithelial immune complex deposition. However, other rare renal presentations have been reported. One of these includes a rapidly progressive glomerulonephritis picture. All described cases have been successfully resolved with the treatment of the underlying syphilis infection. CASE PRESENTATION: The patient was an elderly woman of Caribbean descent who presented with lower extremity weakness, anasarca and proteinuria, hematuria with progressive renal failure. On kidney biopsy, she was found to have a pauci-immune crescentic glomerulonephritis pattern and a concomitant acute tubulointerstitial nephritis. She had a positive Treponema pallidum particle agglutination test and a negative syphilis rapid plasma reagin test with clinical evidence of polyneuropathy suggestive chronic syphilis infection. CONCLUSION AND DISCUSSION: It is important in the context of pauci-immune crescentic glomerulonephritis to explore all differential diagnoses. Given the positive syphilis serologies, clinical context and presence of tubulointerstitial nephritis, she was determined to have syphilitic glomerulonephritis that resolved with a course of both penicillin and steroids.

The metastatic site does not influence PD-L1 expression in advanced non-small cell lung carcinoma.

INTRODUCTION: PD-L1 expression by immunohistochemistry (IHC) testing with Tumor Proportion Score (TPS) ≥50% and ≥1% is required to be eligible for first- and second-line Pembrolizumab treatment for metastatic non-small cell lung cancer (NSCLC) respectively. Stage IV NSCLC often presents with metastasis to multiple distant sites which are easily accessible for biopsy. Knowing whether PD-L1 IHC TPS can be indifferently measured from different metastatic site is therefore an important clinical question. In this study, we evaluated PD-L1 expression in NSCLC from varied distant metastatic sites. METHODS: A total of 580 NSCLC specimens of distant metastases were retrieved for study, including 35 paired samples from two different metastatic sites. The metastatic sites included brain, bone, remote lymph nodes, serous membranes (pleura, pericardium and peritoneum), extra-thoracic solid organs and skin/soft tissues. The samples were cytology cell blocks, small biopsies or surgical resections. IHC was performed using Dako PD-L1 IHC 22C3 pharmDx. A total of 100 viable tumor cells was required for adequacy. TPS ≥ 50% and 1-49% were defined as high and low PD-L1 expression respectively. RESULTS: PD-L1 TPS scores were not significantly different across a range of distant metastatic sites nor between metastases in paired samples. CONCLUSION: Our results suggest that the PD-L1 TPS scoring is similar across different metastatic sites and any site biopsied will yield necessary information for guiding clinical management.

Cytology cell blocks are suitable for immunohistochemical testing for PD-L1 in lung cancer.

Background: PD-L1 immunohistochemistry (IHC) testing is usually carried out on tissue blocks from core needle biopsy or surgical resections. In this study, we assessed the feasibility of using cytology cell blocks for PD-L1 IHC assay. Methods: A total of 1419 consecutive cases of non-small-cell lung cancer (NSCLC), including 371 cytology cell blocks, 809 small biopsies, and 239 surgical specimens, were included in the study. The cytology cell blocks were prepared with formalin only, methanol/alcohol only or both. PD-L1 expression was examined by staining with Dako PD-L1 IHC 22C3 pharmDx kit. A Tumor Proportion Score (TPS) was categorized as <1%, 1%-49% and ≥50% tumor cells. A total of 100 viable tumor cells were required for adequacy. Results: Of the cytology cell blocks, 92% of the specimens had an adequate number of tumor cells, not significantly different from small biopsies. The rate of TPS ≥50% differed between sample types and was observed in 42% of cytology cell blocks versus 36% of small biopsies (P = 0.04), and 29% of surgical resections (P = 0.001). The fixative methods did not affect the immunostaining, with overall PD-L1 high expression (TPS ≥50%) rates of 42% in formalin-fixed specimens versus 40% in specimens with combined fixation by methanol/alcohol and formalin (NS). The PD-L1 high expression rate was not associated with EGFR, ALK or KRAS molecular alterations. Higher stage (IV) was associated with higher PD-L1 TPS (P= 0.001). Conclusion: Our results show that when the TPS ≥50% is used as the end point, PD-L1 IHC performs well with cytology cell blocks. Cell blocks should be considered as a valuable resource for PD-L1 testing in advanced NSCLC. The clinical significance of higher PD-L1 IHC scores in cytology specimens needs to be evaluated prospectively.

Critical involvement of the thalamus and precuneus during restoration of consciousness with physostigmine in humans during propofol anaesthesia: a positron emission tomography study.

BACKGROUND: Functional brain imaging offers a way to investigate how general anaesthetics impair consciousness. However, functional imaging changes may result from drug effects unrelated to hypnosis. Establishing a causal link with loss of consciousness is thus difficult. METHODS: To identify changes of neuronal activity functionally linked to the level of consciousness, physostigmine was used to restore consciousness without changing the anaesthetic concentration in 11 subjects anaesthetized with propofol. Eight subjects (responders) regained consciousness after physostigmine and three did not (non-responders). Positron emission tomography was used to measure regional cerebral blood flow (rCBF); during baseline (awake), after anaesthesia-induced loss of consciousness, after physostigmine administration, and recovery. In addition to subtraction analyses, we used conjunction analysis in the responders to identify changes common to the baseline-anaesthesia and physostigmine-anaesthesia contrasts. RESULTS: Complete data were available for seven subjects (four responders and three non-responders). The analyses revealed that unconsciousness was associated with rCBF decreases in the thalamus and precuneus. Restoration of consciousness by physostigmine was associated with rCBF increases in these same structures, with the strongest effect in the thalamus. CONCLUSIONS: The results provide strong evidence that reductions in rCBF in the thalamus and precuneus are functionally related to propofol-induced unconsciousness independently of any non-specific effects of propofol. These observations confirm that the thalamus and precuneus are key elements to understand how general anaesthetics cause unconsciousness and how patients wake up from anaesthesia. Furthermore, they are consistent with the notion that anaesthetic-induced unconsciousness is associated with reduced cholinergic activation.

Children with atopic histories exhibit impaired lipopolysaccharide-induced Toll-like receptor-4 signalling in peripheral monocytes.

BACKGROUND: The hygiene hypothesis states that early exposure to bacterial products such as lipopolysaccharide (LPS) may be protective against the development of allergic diseases. Whether atopic disease affects the ability of immune cells to respond to LPS is unclear. Our laboratory has demonstrated previously that children express high levels of Toll-like receptor (TLR)-4 on CD4(+) cells in nasal mucosa. OBJECTIVE: To determine if children with a history of allergic disease have impaired responses to LPS on circulating CD4(+) leucocytes. METHODS: Peripheral blood mononuclear cells from children (aged 2-18) and adults with or without a history of atopic conditions were cultured with/without IL-4 or LPS for up to 24 h. Expression of surface TLR-4, CD14, CD4, CD3, as well as of intracellular phosphorylated (p42/p44) ERK and p38 mitogen-activated protein kinase (MAPK) were assessed by flow cytometry. RESULTS: A history of atopy in children was associated with impaired LPS-induced TLR-4-dependent phosphorylation of (p42/44) ERK and p38 MAPK by CD4(+) monocytes. Decreased LPS signalling was reproduced by pre-incubation of control cells with recombinant IL-4. LPS stimulation also decreased TLR-4 expression on monocytes from children without atopic histories but not from atopic subjects. CD4(+) T lymphocytes showed limited LPS responsiveness, regardless of atopic status. In contrast with non-atopic children, TLR-4 expression on monocytes of children with atopic histories decreased as a function of age. CONCLUSIONS: This study provides evidence for defective LPS recognition on circulating CD4(+) leucocytes of subjects with atopic histories compared with those from non-atopic children. CD4(+) TLR4(+) monocytes from children with atopic histories failed to phosphorylate MAPKs. Our results suggest that a history of atopic disease is associated with impaired TLR-4-mediated innate immune function compared with non-atopic children.

Signal transducer and activator of transcription 6 down-regulates toll-like receptor-4 expression of a monocytic cell line.

BACKGROUND: Toll-like receptor 4 (TLR4), part of the bacterial lipopolysaccharide (LPS) receptor, is an important bridge between innate and adaptive immunity. Our previous studies have indicated reduced expression of TLR4 and reduced responsiveness to LPS in nasal mucosa of atopic adults compared with non-atopic adults. IL-4 and signal transducer and activator of transcription 6 (STAT6), which are increased in atopic patients, may have a role in modulating TLR4. OBJECTIVE: To examine direct effects of IL-4 and STAT6 on TLR4 expression of U-937 monocytic cells. METHODS: LPS responsiveness, under different conditions of U-937 cells was measured by nuclear factor (NF)-kappaB activation of transcription. TLR4 mRNA was quantified by real-time PCR and TLR4 surface expression was measured by flow cytometry. The promoter and 4.3 kb of the upstream region of TLR4 were cloned into a plasmid vector and transiently transfected into U-937 cells. Transfected cells were incubated with IL-4 and transcriptional activity was assayed by the luciferase assay. STAT6 was transfected to evaluate overexpression of this transcription factor. Cells were also incubated with Tyrphostin AG490 to inhibit tyrosine kinases. RESULTS: NF-kappaB activation by LPS was inhibited by IL-4 pre-incubation but not when IL-4 was added at the same time as LPS. TLR4 mRNA expression was inhibited by IL-4 as early as 6 h but the effect was lost by 24 h. Surface expression of TLR4 was inhibited by IL-4 at 12 and 24 h, but returned to baseline at 48 h. IL-4 inhibited activity of the TLR4 promoter as early as 6 h, but, like the mRNA, these effects were transient. STAT6 overexpression enhanced the inhibition of the TLR4 promoter and prolonged it. Inhibition of TLR4 by IL-4 was abolished by pre-incubation with the tyrosine kinase inhibitor Tyrphostin AG490. CONCLUSION: Our findings demonstrate that IL-4, through STAT6, can modulate TLR4 expression and suggests that Th2 cytokines can impact on the LPS responsiveness of cells.

Increasing blood oxygen increases an index of 5-HT synthesis in human brain as measured using alpha-[(11)C]methyl-L-tryptophan and positron emission tomography.

The main objective of this investigation was to test the hypothesis that brain serotonin (5-HT) synthesis, as measured by trapping of alpha-[(11)C]methyl-L-tryptophan (alpha-MTrp) using positron emission tomography (PET), can be modulated by changes in blood oxygen. The study involved six healthy participants (three male and three female), who breathed a 15% or 60% oxygen mixture starting 15 min before the injection of tracer and continuing during the entire acquisition period. Participants were injected with up to 12m Ci of alpha-MTrp. Two sets of PET images were acquired while the participants were breathing each of the oxygen mixtures and, after reconstruction, all images were converted into brain functional images illustrating the brain trapping constant K(*) (microL/g/min). The K(*) values were obtained for 12 regions of interest outlined on the magnetic resonance images. The K(*) values obtained at high and low blood oxygen content were compared by paired statistics using Tukey's post hoc correction. As there were no difference in plasma tryptophan concentrations, these K(*) values are directly related to regional 5-HT synthesis. The results showed highly significant increases (50% on average) in brain serotonin synthesis (K(*) values) at high (mean value of 223+/-41 mmHg) relative to low (mean value 77.1+/-7.7 mmHg) blood oxygen levels. This suggests that tryptophan hydroxylase is not saturated with oxygen in the living human brain and that increases in blood oxygen can elevate brain serotonin synthesis.

Antagonism of sevoflurane anaesthesia by physostigmine: effects on the auditory steady-state response and bispectral index.

BACKGROUND: Physostigmine, a centrally acting anticholinesterase, antagonizes the hypnotic effect of propofol, as shown by the return of consciousness (response to commands) or wakefulness (spontaneous eye-opening without response to commands) and by recovery of auditory evoked potentials (40 Hz auditory steady-state response (ASSR)) and the bispectral index (BIS). We measured the effects of physostigmine on the hypnotic effect of inhaled volatile anaesthetics, using sevoflurane as the representative agent. METHODS: Eight healthy volunteers received sevoflurane adjusted to produce loss of consciousness. Physostigmine (plus glycopyrrolate) was given while the end-tidal concentration of sevoflurane was kept constant. RESULTS: Loss of consciousness was accompanied by a significant (P<0.02) decrease in ASSR amplitude (to 21% of awake value) and BIS (to 70% of awake value). Five subjects had return of consciousness or wakefulness after physostigmine. The others showed no behavioural change. Physostigmine caused a significant increase of the mean ASSR amplitude from 0.11 (SD 0.04) to 0.17 (0.06) microV (P<0.05). The BIS also increased, from 66 (12) to 74 (12), but the difference was not significant. CONCLUSIONS: Physostigmine can antagonize, at least partially, the hypnotic effect of sevoflurane and changes in arousal after physostigmine are shown by ASSR measurements. However, the antagonism is not as clear or reliable as with propofol.

Integrated analysis of protein and glucose metabolism during surgery: effects of anesthesia.

The aim of this study was to assess dynamic changes in protein and glucose metabolism during surgery. Twelve patients undergoing colorectal surgery received either intravenous propofol anesthesia (n = 6) or inhalational anesthesia with desflurane (n = 6). Pre- and intraoperative protein and glucose kinetics were analyzed by an isotope dilution technique using L-[1-(13)C]leucine and [6,6-(2)H(2)]glucose. Plasma concentrations of glucose, lactate, free fatty acids, insulin, glucagon, and cortisol were measured before and after 2 h of surgery. The rates of appearance of leucine and glucose, leucine oxidation, protein synthesis, and glucose clearance decreased during surgery, independent of the type of anesthesia (P < 0.05). A correlation between the rate of appearance of leucine and glucose was observed (r = 0.755, P < 0.001). Intraoperative plasma cortisol and glucose concentrations increased (P < 0.05), whereas plasma concentrations of lactate, free fatty acids, insulin, and glucagon did not change. Surgery causes a depression of whole body protein and glucose metabolism, independent of the anesthetic technique. There is a correlation between perioperative glucose production and protein breakdown.

Propofol anesthesia and cerebral blood flow changes elicited by vibrotactile stimulation: a positron emission tomography study.

We investigated the effects of the general anesthetic agent propofol on cerebral structures involved in the processing of vibrotactile information. Using positron emission tomography (PET) and the H(2)(15)O bolus technique, we measured regional distribution of cerebral blood flow (CBF) in eight healthy human volunteers. They were scanned under five different levels of propofol anesthesia. Using a computer-controlled infusion, the following plasma levels of propofol were targeted: Level W (Waking, 0 microg/ml), Level 1 (0.5 microg/ml), Level 2 (1.5 microg/ml), Level 3 (3.5 microg/ml), and Level R (Recovery). At each level of anesthesia, two 3-min scans were acquired with vibrotactile stimulation of the right forearm either on or off. The level of consciousness was evaluated before each scan by the response of the subject to a verbal command. At Level W, all volunteers were fully awake. They reported being slightly drowsy at Level 1, they had a slurred speech and slow response at Level 2, and they were not responding at all at Level 3. The following variations in regional CBF (rCBF) were observed. During the waking state (Level W), vibrotactile stimulation induced a significant rCBF increase in the left thalamus and in several cortical regions, including the left primary somatosensory cortex and the left and right secondary somatosensory cortex. During anesthesia, propofol reduced in a dose-dependent manner rCBF in the thalamus as well as in a number of visual, parietal, and prefrontal cortical regions. At Level 1 through 3, propofol also suppressed vibration-induced increases in rCBF in the primary and secondary somatosensory cortex, whereas the thalamic rCBF response was abolished only at Level 3, when volunteers lost consciousness. We conclude that propofol interferes with the processing of vibrotactile information first at the level of the cortex before attenuating its transfer through the thalamus.

Auditory steady-state response and bispectral index for assessing level of consciousness during propofol sedation and hypnosis.

UNLABELLED: We assessed the effect of propofol on the auditory steady-state response (ASSR), bispectral (BIS) index, and level of consciousness in two experiments. In Experiment 1, propofol was infused in 11 subjects to obtain effect-site concentrations of 1, 2, 3, and 4 microg/mL. The ASSR and BIS index were recorded during baseline and at each concentration. The ASSR was evoked by monaural stimuli. Propofol caused a concentration-dependent decrease of the ASSR and BIS index values (r(2) = 0.76 and 0.93, respectively; P<0.0001). The prediction probability for loss of consciousness was 0.89, 0.96, and 0.94 for ASSR, BIS, and arterial blood concentration of propofol, respectively. In Experiment 2, we compared the effects of binaural versus monaural stimulus delivery on the ASSR in six subjects during awake baseline and propofol-induced unconsciousness. During baseline, the ASSR amplitude with binaural stimulation (0.47+/-0.13 microV, mean +/- SD) was significantly (P<0.002) larger than with monaural stimulation (0.35+/-0.11 microV). During unconsciousness, the amplitude was 0.09+/-0.09 microV with monaural and 0.06+/-0.04 microV with binaural stimulation (NS). The prediction probability for loss of consciousness was 0.97 (0.04 SE) for monaural and 1.00 (0.00 SE) for binaural delivery. We conclude that the ASSR and BIS index are attenuated in a concentration-dependent manner by propofol and provide a useful measure of its sedative and hypnotic effect. BIS was easier to use and slightly more sensitive. The ASSR should be recorded with binaural stimulation. The ASSR and BIS index are both useful for assessing the level of consciousness during sedation and hypnosis with propofol. However, the BIS index was simpler to use and provided a more sensitive measure of sedation. IMPLICATIONS: We have compared two methods for predicting whether the amount of propofol given to a human subject is sufficient to cause unconsciousness, defined as failure to respond to a simple verbal command. The two methods studied are the auditory steady-state response, which measures the electrical response of the brain to sound, and the bispectral index, which is a number derived from the electroencephalogram. The results showed that both methods are very good predictors of the level of consciousness; however, bispectral was easier to use.

Physostigmine reverses propofol-induced unconsciousness and attenuation of the auditory steady state response and bispectral index in human volunteers.

BACKGROUND: It is postulated that alteration of central cholinergic transmission plays an important role in the mechanism by which anesthetics produce unconsciousness. The authors investigated the effect of altering central cholinergic transmission, by physostigmine and scopolamine, on unconsciousness produced by propofol. METHODS: Propofol was administered to American Society of Anesthesiologists physical status 1 (n = 17) volunteers with use of a computer-controlled infusion pump at increasing concentrations until unconsciousness resulted (inability to respond to verbal commands, abolition of spontaneous movement). Central nervous system function was assessed by use of the Auditory Steady State Response (ASSR) and Bispectral Index (BIS) analysis of electrooculogram. During continuous administration of propofol, reversal of unconsciousness produced by physostigmine (28 microgram/kg) and block of this reversal by scopolamine (8.6 microgram/kg) were evaluated. RESULTS: Propofol produced unconsciousness at a plasma concentration of 3.2 +/- 0.8 (+/- SD) microgram/ml (n = 17). Unconsciousness was associated with reductions in ASSR (0.10 +/- 0.08 microV [awake baseline 0.32 +/- 0.18 microV], P < 0.001) and BIS (55.7 +/- 8.8 [awake baseline 92.4 +/- 3.9], P < 0.001). Physostigmine restored consciousness in 9 of 11 subjects, with concomitant increases in ASSR (0.38 +/- 0.17 microV, P < 0.01) and BIS (75.3 +/- 8.3, P < 0.001). In all subjects (n = 6) scopolamine blocked the physostigmine-induced reversal of unconsciousness and the increase of the ASSR and BIS (ASSR and BIS during propofol-induced unconsciousness: 0.09 +/- 0.09 microV and 58.2 +/- 7.5, respectively; ASSR and BIS after physostigmine administration: 0.08 +/- 0.06 microV and 56.8 +/- 6.7, respectively, NS). CONCLUSIONS: These findings suggest that the unconsciousness produced by propofol is mediated at least in part via interruption of central cholinergic muscarinic transmission.

Enhancement of the signal-to-noise ratio in H2(15)O bolus PET activation images: a combined cold-bolus, switched protocol.

UNLABELLED: To increase the signal-to-noise ratio (S/N) of H2(15)O bolus PET activation images, we designed and tested a data acquisition protocol that alters the relative distribution of tracer in the uptake and washout phases of the input function. This protocol enhances the S/N gains obtained with conventional switched protocols by combining task switching and the use of a large bolus of blood free of tracer (cold bolus). The cold bolus is formed by sequestering blood in the lower limbs with a double cuff before tracer injection. METHODS: The effect of a combined cold-bolus, switched protocol on the signal from activation images was first simulated using a compartmental model of the uptake of H2(15)O into the brain. Then, the effectiveness of the protocol was investigated in 4 healthy volunteers performing a language task. Each volunteer underwent scanning 12 times: 3 activation/ baseline and 3 baseline/activation scans using the conventional switched protocol and 3 activation/baseline and 3 baseline/activation scans using the combined cold-bolus, switched protocol. The S/N changes introduced when using the cold bolus were analyzed by comparing, across protocols, the magnitude and statistical significance of the activation foci associated with the execution of the language task identified in the averaged subtracted images, and by comparing image noise levels. RESULTS: In the simulated datasets, the combined protocol yielded a substantial increase in the activation signals for scan durations greater than 60 s, in comparison with equivalent signals yielded by the switched protocol alone. In the PET experiments, activation foci obtained using the combined protocol had significantly higher t statistic values than did equivalent foci detected using the conventional switched protocol (mean improvement, 36%). Analysis of the S/N in the averaged subtracted images revealed that the improvements in statistical significance of the activation foci were caused by increases in the signal magnitudes and not by decreases in overall image noise. CONCLUSION: We designed a data acquisition protocol for H2(15)O bolus PET activation studies that combines the use of a tracer-free bolus with a switched protocol. Simulated and experimental data suggest that this combined protocol enhances the S/N gains obtained with a conventional switched protocol. Implementation of the combined protocol in H2(15)O bolus activation studies was easy.

Brain mechanisms of propofol-induced loss of consciousness in humans: a positron emission tomographic study.

In the present study, we used positron emission tomography to investigate changes in regional cerebral blood flow (rCBF) during a general anesthetic infusion set to produce a gradual transition from the awake state to unconsciousness. Five right-handed human volunteers participated in the study. They were given propofol with a computer-controlled infusion pump to achieve three stable levels of plasma concentrations corresponding to mild sedation, deep sedation, and unconsciousness, the latter defined as unresponsiveness to verbal commands. During awake baseline and each of the three levels of sedation, two scans were acquired after injection of an H215O bolus. Global as well as regional CBF were determined and correlated with propofol concentrations. In addition, blood flow changes in the thalamus were correlated with those of the entire scanned volume to determine areas of coordinated changes. In addition to a generalized decrease in global CBF, large regional decreases in CBF occurred bilaterally in the medial thalamus, the cuneus and precuneus, and the posterior cingulate, orbitofrontal, and right angular gyri. Furthermore, a significant covariation between the thalamic and midbrain blood flow changes was observed, suggesting a close functional relationship between the two structures. We suggest that, at the concentrations attained, propofol preferentially decreases rCBF in brain regions previously implicated in the regulation of arousal, performance of associative functions, and autonomic control. Our data support the hypothesis that anesthetics induce behavioral changes via a preferential, concentration-dependent effect on specific neuronal networks rather than through a nonspecific, generalized effect on the brain.

Pharmacokinetics and pharmacodynamics of cisatracurium after a short infusion in patients under propofol anesthesia.

UNLABELLED: Fourteen patients, ASA physical status I or II, were recruited to assess the pharmacokinetic-pharmacodynamic relationship of cisatracurium under nitrous oxide/sufentanil/propofol anesthesia. The electromyographic response of the abductor digiti minimi muscle was recorded on train-of-four stimulation of the ulnar nerve. A 0.1-mg/kg dose of cisatracurium was given as an infusion over 5 min. Arterial plasma concentrations of cisatracurium and its major metabolites were measured by using high-performance liquid chromatography. A nontraditional two-compartment pharmacokinetic model with elimination from central and peripheral compartments was used. The elimination rate constant from the peripheral compartment was fixed to the in vitro rate of degradation of cisatracurium in human plasma (0.0237 min(-1)). The mean terminal half-life of cisatracurium was 23.9+/-3.3 min, and its total clearance averaged 3.7+/-0.8 mL x min(-1) x kg(-1). Using this model, the volume of distribution at steady state was significantly increased compared with that obtained when central elimination only was assumed (0.118+/-0.027 vs 0.089+/-0.017 L/kg). The effect-plasma equilibration rate constant was 0.054+/-0.013 min(-1). The 50% effective concentration (153+/-33 ng/mL) was 56% higher than that reported in patients anesthetized with volatile anesthetics, which suggests that, compared with inhaled anesthetics, a cisatracurium neuromuscular block is less enhanced by propofol. IMPLICATIONS: The drug concentration-effect relationship of the muscle relaxant cisatracurium has been characterized under balanced and isoflurane anesthesia. Because propofol is now widely used as an IV anesthetic, it is important to characterize the biological fate and the concentration-effect relationship of cisatracurium under propofol anesthesia as well.