Preoperative Midazolam and Patient-Centered Outcomes of Older Patients: The I-PROMOTE Randomized Clinical Trial.

Importance: The effect of oral midazolam premedication on patient satisfaction in older patients undergoing surgery is unclear, despite its widespread use. Objective: To determine the differences in global perioperative satisfaction in patients with preoperative administration of oral midazolam compared with placebo. Design, Setting, and Participants: This double-blind, parallel-group, placebo-controlled randomized clinical trial was conducted in 9 German hospitals between October 2017 and May 2019 (last follow-up, June 24, 2019). Eligible patients aged 65 to 80 years who were scheduled for elective inpatient surgery for at least 30 minutes under general anesthesia and with planned extubation were enrolled. Data were analyzed from November 2019 to December 2020. Interventions: Patients were randomized to receive oral midazolam, 3.75 mg (n = 309), or placebo (n = 307) 30 to 45 minutes prior to anesthesia induction. Main Outcomes and Measures: The primary outcome was global patient satisfaction evaluated using the self-reported Evaluation du Vécu de l'Anesthésie Generale (EVAN-G) questionnaire on the first postoperative day. Key secondary outcomes included sensitivity and subgroup analyses of the primary outcome, perioperative patient vital data, adverse events, serious complications, and cognitive and functional recovery up to 30 days postoperatively. Results: Among 616 randomized patients, 607 were included in the primary analysis. Of these, 377 (62.1%) were male, and the mean (SD) age was 71.9 (4.4) years. The mean (SD) global index of patient satisfaction did not differ between the midazolam and placebo groups (69.5 [10.7] vs 69.6 [10.8], respectively; mean difference, -0.2; 95% CI, -1.9 to 1.6; P = .85). Sensitivity (per-protocol population, multiple imputation) and subgroup analyses (anxiety, frailty, sex, and previous surgical experience) did not alter the primary results. Secondary outcomes did not differ, except for a higher proportion of patients with hypertension (systolic blood pressure ≥160 mm Hg) at anesthesia induction in the placebo group. Conclusion and Relevance: A single low dose of oral midazolam premedication did not alter the global perioperative patient satisfaction of older patients undergoing surgery or that of patients with anxiety. These results may be affected by the low dose of oral midazolam. Further trials-including a wider population with commonplace low-dose intravenous midazolam and plasma level measurements-are needed. Trial Registration: ClinicalTrials.gov Identifier: NCT03052660.

Hemodynamic monitoring with Hypotension Prediction Index versus arterial waveform analysis alone and incidence of perioperative hypotension.

BACKGROUND: Intraoperative hypotension is associated with increased morbidity and mortality. The Hypotension Prediction Index (HPI) is an advancement of the arterial waveform analysis to predict intraoperative hypotension minutes before episodes occur enabling preventive treatments. We tested the hypothesis that the HPI combined with a personalized treatment protocol reduces intraoperative hypotension when compared to arterial waveform analysis alone. METHODS: We conducted a retrospective analysis of 100 adult consecutive patients undergoing moderate- or high-risk noncardiac surgery with invasive arterial pressure monitoring using either index guidance (HPI) or arterial waveform analysis (FloTrac) depending on availability (FloTrac, n = 50; HPI, n = 50). A personalized treatment protocol was applied in both groups. The primary endpoint was the incidence and duration of hypotensive events defined as MAP <65 mmHg evaluated by time-weighted average of hypotension. RESULTS: In the FloTrac group, 42 patients (84%) experienced a hypotension while in the HPI group 26 patients (52%) were hypotensive (p = 0.001). The median (IQR) time-weighted average of hypotension in the FloTrac group was 0.27 (0.42) mmHg versus 0.10 (0.19) mmHg in the HPI group (p = 0.001). Finally, the median duration of each hypotensive event (IQR) was 2.75 (2.40) min in the FloTrac group compared to 1.00 (2.06) min in the HPI group (p = 0.002). CONCLUSIONS: The application of the HPI combined with a personalized treatment protocol can reduce incidence and duration of hypotension when compared to arterial waveform analysis alone. This study therefore provides further evidence of the transition from prediction to actual prevention of hypotension using HPI.

Randomized controlled multicentre study of albumin replacement therapy in septic shock (ARISS): protocol for a randomized controlled trial.

BACKGROUND: Albumin is a key regulator of fluid distribution within the extracellular space and has several properties beyond its oncotic activity. The accumulating evidence suggests that supplementation of albumin may provide survival advantages only when the insult is severe as in patients with septic shock. METHODS/DESIGN: The randomized controlled multicentre study of albumin replacement therapy in septic shock (ARISS) investigates whether the replacement with albumin and the maintenance of its serum levels of at least 30 g/l for 28 days improve survival in patients with septic shock compared to resuscitation and volume maintenance without albumin. Adult patients (≥ 18 years) with septic shock are randomly assigned within a maximum of 24 h after the onset of septic shock after obtaining informed consents to treatment or control groups. Patients assigned to the treatment group receive a 60-g loading dose of human albumin 20% over 2-3 h. Serum albumin levels are maintained at least at 30 g/l in the ICU for a maximum of 28 days following randomization using 40-80 g human albumin 20% infusion. The control group is treated according to the usual practice with crystalloids as the first choice for the resuscitation and maintenance phase of septic shock. The primary endpoint is 90 days mortality and secondary endpoints include 28-day, 60-day, ICU, and in-hospital mortality, organ dysfunction/failure, total amount of fluid administration and total fluid balance in the ICU, and lengths of ICU and hospital stay. In total, 1412 patients need to be analysed, 706 per group. For the sample size estimation, a 15% reduction in 90-day mortality is assumed, i.e. an absolute reduction of 7.5% points to 42.5% (relative risk 1.18). Assuming a dropout rate of 15%, a total of 1662 patients need to be allocated. DISCUSSION: The results of the clinical trial may influence the treatment of patients with septic shock. The expected improvement in patient survival may result in a reduction in the resources currently used in the treatment of these patients and in the socioeconomic burden of this disease. TRIAL REGISTRATION: ClinicalTrials.gov NCT03869385 . Registration on 18 July 2019. Protocol version: Final 3.0.

Impact of PReOperative Midazolam on OuTcome of Elderly patients (I-PROMOTE): study protocol for a multicentre randomised controlled trial.

INTRODUCTION: Premedication of surgical patients with benzodiazepines has become questionable regarding risk-benefit ratio and lack of evidence. Though preoperative benzodiazepines might alleviate preoperative anxiety, a higher risk for adverse events is described, particularly for elderly patients (≥ 65 years). Several German hospitals already withhold benzodiazepine premedication from elderly patients, though evidence for this approach is lacking. The patient-centred outcome known as global postoperative patient satisfaction is recognised as a substantial quality indicator of anaesthesia care incorporated by the American Society of Anesthesiologists. Therefore, we aim to assess whether the postoperative patient satisfaction after premedication with placebo compared to the preoperative administration of 3.75 mg midazolam in elderly patients differs. METHODS: This study is a multicentre, randomised, placebo-controlled, double-blinded, two-arm parallel, interventional trial, conducted in nine German hospitals. In total 614 patients (≥ 65-80 years of age) undergoing elective surgery with general anaesthesia will be randomised to receive either 3.75 mg midazolam or placebo. The primary outcome (global patient satisfaction) will be assessed with the validated EVAN-G questionnaire on the first postoperative day. Secondary outcomes will be assessed until the first postoperative day and then 30 days after surgery. They comprise among other things: functional and cognitive recovery, postoperative delirium, health-related quality of life assessment, and mortality or new onset of serious cardiac or pulmonary complications, acute stroke, or acute kidney injury. Analysis will adhere to the intention-to-treat principle. The primary outcome will be analysed with the use of mixed linear models including treatment effect and study centre as factors and random effects for blocks. Exploratory adjusted and subgroup analyses of the primary and secondary outcomes with regard to gender effects, frailty, pre-operative anxiety level, patient demographics, and surgery experience will also be performed. DISCUSSION: This is, to the best of our knowledge, the first study analysing patient satisfaction after premedication with midazolam in elderly patients. In conclusion, this study will provide high-quality data for the decision-making process regarding premedication in elderly surgical patients. TRIAL REGISTRATION: ClinicalTrials.gov, NCT03052660 . Registered on 14 February 2017. EudraCT 2016-004555-79 .

Association between the Surgical Apgar Score and Perioperative Complications after Radical Prostatectomy.

OBJECTIVE: To evaluate whether the Surgical Apgar Score (SAS) can identify patients who are at risk for perioperative adverse events (PAE) following radical prostatectomy for prostate cancer. PATIENTS AND METHODS: At a single academic institution, 994 patients undergoing radical prostatectomy between 2010 and 2013 were analyzed retrospectively. The SAS was calculated from anesthesia records, evaluated to predict PAE within a 30-day time period postoperatively; these events were classified according to standardized classification systems. RESULTS: We observed adverse events in 45.4% (451/994) of patients with a total of 694 events. Overall, 41% (408/994) had low- and 9.9% (98/994) had high-grade events. A lower SAS was identified as an independent predictor of any (p < 0.001) and low-grade adverse events (p = 0.001) for those patients who had undergone open retropubic radical prostatectomy (ORRP). Each 1-point increment resulted in a 24% decrease in the odds of any (95% CI 0.66-0.88) and a 21% decrease in the odds of a low-grade (95% CI 0.69-0.91) event. Adverse events of robot-assisted prostatectomy were not associated with the SAS. CONCLUSIONS: Lower SAS values indicate patients at risk for adverse events after ORRP. The SAS might serve as one variable for outcome assessment, reflecting the challenge of mutual surgical and anesthesiology procedure management.

Monitoring depth of anesthesia utilizing a combination of electroencephalographic and standard measures.

BACKGROUND: For decades, monitoring depth of anesthesia was mainly based on unspecific effects of anesthetics, for example, blood pressure, heart rate, or drug concentrations. Today, electroencephalogram-based monitors promise a more specific assessment of the brain function. To date, most approaches were focused on a "head-to-head" comparison of either electroencephalogram- or standard parameter-based monitoring. In the current study, a multimodal indicator based on a combination of both electro encephalographic and standard anesthesia monitoring parameters is defined for quantification of "anesthesia depth." METHODS: Two hundred sixty-three adult patients from six European centers undergoing surgery with general anesthesia were assigned to 1 of 10 anesthetic combinations according to standards of the enrolling hospital. The anesthesia multimodal index of consciousness was developed using a data-driven approach, which maps standard monitoring and electroencephalographic parameters into an output indicator that separates different levels of anesthesia from awake to electroencephalographic burst suppression. Obtained results were compared with either a combination of standard monitoring parameters or the electroencephalogram-based bispectral index. RESULTS: The anesthesia multimodal index of consciousness showed prediction probability (P(K)) of 0.96 (95% CI, 0.95 to 0.97) to separate different levels of anesthesia (wakefulness to burst suppression), whereas the bispectral index had significantly lower PK of 0.80 (0.76 to 0.81) at corrected threshold P value of less than 0.05. At the transition between consciousness and unconsciousness, anesthesia multimodal index of consciousness yielded a PK of 0.88 (0.85 to 0.91). CONCLUSION: A multimodal integration of both standard monitoring and electroencephalographic parameters may more precisely reflect the level of anesthesia compared with monitoring based on one of these aspects alone.

Awareness under general anesthesia.

BACKGROUND: Awareness while under general anesthesia, and the later recall of what happened during surgery, can be experienced by patients as horrific events that leave lasting mental trauma behind. Patients may have both auditory and tactile perception, potentially accompanied by feelings of helplessness, inability to move, pain, and panic ranging to an acute fear of death. For some patients, the experience of awareness under anesthesia has no sequelae; for others, however, it can lead to the development of post-traumatic stress disorder, consisting of complex psychopathological phenomena such as anxiety, insomnia, nightmares, irritability, and depression possibly leading to suicidality. METHODS: The literature on the subject was selectively reviewed. RESULTS: In the absence of risk factors awareness phenomena occur in one to two per 1000 operations under general anesthesia (0.1% to 0.2%) and are thus classed as an occasionally occurring critical event. In children, the risk of such phenomena occurring is 8 to 10 times higher. These phenomena are due to an inadequate depth of anesthesia with incomplete unconsciousness. They can be promoted by a number of risk factors that are either patient-related (ASA class III or above, medication abuse), surgery-related (Caesarean section, emergency procedures, surgery at night), or anesthesia-related (anesthesia without benzodiazepines, use of muscle relaxants). CONCLUSION: Strategies for avoiding awareness phenomena under anesthesia include the training of staff to know about the problem and, specifically, the use of benzodiazepines, the avoidance of muscle relaxants if possible, and shielding the patient from excessive noise. EEG monitoring is effective but provides no guarantee against awareness. If awareness under anesthesia occurs despite these measures, the patient must be given expert, interdisciplinary treatment as soon after the event as possible in order to minimize its potential sequelae.

The experience of relatives asked for organ donation. The original project, obstacles, findings, and unexpected results.

In this article we describe the aims of a Swiss cohort study in bereaved relatives who were asked for organ donation. Their experience in the ICU was assessed six months after the donation request by questionnaire (quantitative approach) and, in a subgroup, by interviews (qualitative approach). The difficulties of running such a multitcentre study are reported in detail. A short overview of general findings is given. The unexpected results, namely the impact of our findings on communication skills training in ICU staffs, and the change engendered in the clinical practice of transplantation coordinators in the follow-up of donor families, are described in detail.

Identification of sensory blockade by somatosensory and pain-induced evoked potentials.

BACKGROUND: To date, the anesthesia-induced blockade of nociceptive inputs is insufficiently reflected by commercially available electroencephalographic depth-of-anesthesia monitors. The aim of the current study was to evaluate the potential of somatosensory (SSEP) and intracutaneous pain evoked (iSEP) potentials during remifentanil and propofol anesthesia as electroencephalographic indicators of the nociceptive blockade. METHODS: Ten healthy men were investigated in a double-blind crossover design during three sessions with remifentanil, propofol, and placebo administration. All dosages were increased in a step-by-step mode. SSEP and iSEP recordings were performed followed by subjective pain ratings and measurement of level of sedation (modified Observer's Assessment of Alertness and Sedation Scale). Changes from baseline in evoked potential components, pain ratings, and sedation scale were assessed by Bonferroni-Holms-corrected Wilcoxon tests. RESULTS: Pain ratings were significantly reduced by remifentanil. Sedation scale was significantly reduced by propofol. Early SSEP components were not affected by medication. The amplitudes of the long latency SSEP components increased significantly with remifentanil, decreased with propofol, and did not change with placebo. The amplitudes of long latency components of the iSEP decreased significantly with both remifentanil and propofol and did not change with placebo. CONCLUSION: Long latency components of the SSEP are differently affected by remifentanil and propofol administration. Further studies are needed to clarify whether they can serve as a specific indicator of the nociceptive blockade during anesthesia.

Clonidine effects on pain evoked SII activity in humans.

We investigated pain evoked activity in the human secondary sensory cortex (SII) following clonidine administration in six healthy volunteers using multi-channel magnetoencephalography (MEG). Pain was elicited by electrical shocks applied intracutaneously to the fingertip. Subjects rated pain intensity and perceptions of tiredness and passiveness by numerical ranking scales. Each subject underwent two investigations, one week apart from each other, with clonidine doses of 1.5 or 3.0microg/kg, administered intravenously in a random order and double-blinded. We applied a total number of seven blocks, each consisting of 60 painful stimuli, with one adaptation block, one pre-medication block, four post-medication blocks and one recovery block at the end of the session. MEG data were analysed by dipole reconstruction using CURRY(R) (Neuroscan, Hamburg) software package. Cortical activity in the contralateral SII cortex appeared with peak latencies of 118.5+/-10ms. This activity was significantly reduced by clonidine, in parallel with a reduction of pain intensity and enhancement of subjective tiredness and passiveness. There was, however, no significant correlation between MEG and subjective effects. Although both clonidine doses had similar effects, the higher dose induced longer changes. Results indicate that intravenous clonidine is able to relieve pain, but the exact mechanism of clonidine at the level of the SII cortex remains unclear. It is possible that clonidine interacts with the brainstem ascending system regulating vigilance and arousal which would explain the observed decrement of pain induced activity in SII. An additional more specific analgesic action at spinal level cannot be excluded.

Comparative evaluation of the Datex-Ohmeda S/5 Entropy Module and the Bispectral Index monitor during propofol-remifentanil anesthesia.

BACKGROUND: Different analytical concepts were introduced to quantify the changes of the electroencephalogram. The Datex-Ohmeda S/5 Entropy Module (Datex-Ohmeda Division, Instrumentarium Corp., Helsinki, Finland) was the first commercial monitor based on the entropy generating two indices, the state entropy (SE) and the response entropy (RE). The aim of the current study was to compare the accuracy of SE and RE with the Bispectral Index(R) monitor (BIS(R); Aspect Medical Systems, Newton, MA) during propofol-remifentanil anesthesia. METHODS: The authors investigated 20 female patients during minor gynecologic surgery. SE, RE, BIS, mean arterial blood pressure, heart rate, and sedation level were recorded every 20 s during stepwise increase (target-controlled infusion, 0.5 microg/ml) of propofol until the patients lost response. Five minutes after loss of response, remifentanil infusion (0.4 microg . kg(-1) . min(-1)) was started. Spearman correlation coefficient and prediction probability were calculated for sedation levels with SE, RE, BIS, mean arterial blood pressure, and heart rate. The ability of the investigated parameters to distinguish between the anesthesia steps awake versus loss of response, awake versus anesthesia, anesthesia versus first reaction, and anesthesia versus extubation was analyzed with the prediction probability. RESULTS: SE correlates best with sedation levels, but no significant differences of the prediction probability values among SE, RE, and BIS were found. The prediction probability for all investigated steps of anesthesia did not show significant differences among SE, RE, and BIS. SE, RE, and BIS were superior to mean arterial blood pressure and heart rate. CONCLUSION: SE, RE, and BIS revealed similar information about the level of sedation and allowed the authors to distinguish between different steps of anesthesia. Both monitors provided useful additional information for the anesthesiologist.

Comparative evaluation of Narcotrend, Bispectral Index, and classical electroencephalographic variables during induction, maintenance, and emergence of a propofol/remifentanil anesthesia.

UNLABELLED: In the present study, we sought to compare the abilities of Narcotrend (NT) with the Bispectral Index (BIS) electroencephalographic system to monitor depth of consciousness immediately before induction of anesthesia until extubation during a standardized anesthetic. We investigated 26 patients undergoing laminectomy. Investigated states of anesthesia were: awake, loss of response, loss of eyelash reflex, steady-state anesthesia, first reaction, and extubation during emergence. NT, BIS, spectral edge frequency, median frequency, relative power in delta, theta, alpha, beta, and hemodynamics were recorded simultaneously. The ability of all variables to distinguish between awake versus loss of response, awake versus loss of eyelash reflex, awake versus steady-state anesthesia, steady-state anesthesia versus first reaction and extubation were analyzed with the prediction probability. Effects of remifentanil during propofol infusion were investigated with Friedman's and post hoc with Wilcoxon's test. Only NT and BIS were able to distinguish all investigated states accurately with a prediction probability >0.95. After start of remifentanil infusion, only hemodynamics changed statistically significantly (P < 0.05). NT and BIS are more reliable indicators for the assessment of anesthetic states than classical electroencephalographic variables and hemodynamics, whereas the analgesic potency of depth of anesthesia could not be detected by NT and BIS. IMPLICATIONS: The modern electroencephalographic monitoring systems Narcotrend and Bispectral Index are more reliable indicators for the assessment of anesthetic states than classical electroencephalographic and hemodynamic variables to predict anesthetic conditions from before induction of anesthesia until extubation during a standardized anesthetic regime with propofol and remifentanil. The analgesic potency of depth of anesthesia could not be detected by Narcotrend and Bispectral Index.

Epidural hematoma after spinal anesthesia in a patient with undiagnosed epidural lymphoma.

UNLABELLED: The incidence of hemorrhagic complications after neuroaxial anesthesia is very infrequent. We report a case of a woman developing epidural bleeding 3 wk after performing an uneventful spinal anesthesia at the lumbar level L3-4 for removal of a wire loop in her left knee. No hemostasis altering medication had been taken before and after spinal puncture. The hematoma presenting at the lumbar level L2-3 had to be removed via laminectomy. Pathological examination of the hematoma revealed a highly vascularized centroblastic non-Hodgkin's lymphoma that was not diagnosed before surgery. The patient did not develop any neurological deficits. IMPLICATIONS: We report a case of a women developing epidural bleeding 3 wk after performing an uneventful spinal anesthesia for removal of a wire loop in her left knee. Pathological examination of the neurosurgically removed hematoma revealed a highly vascularized epidural centroblastic non-Hodgkin lymphoma.

Detection of clinically relevant antibiotic-resistance genes in municipal wastewater using real-time PCR (TaqMan).

Real-time PCR assays were developed for the quantifiable detection of the antibiotic-resistance genes vanA of enterococci, ampC of Enterobacteriaceae, and mecA of staphylococci in different municipal wastewater samples. Primer and probe designs for these resistance genes were constructed and optimised for application in standardised TaqMan PCR assays. Using reference strains, the linear measurement ranges of the assays were defined and covered concentration ranges of five to seven exponential values. Wastewater isolates of vancomycin-resistant enterococci (VRE) and beta-lactam-resistant Enterobacteriaceae were cultivated from municipal wastewaters in order to verify the specificity and sensitivity of the primer-probe systems. Additionally, clinical strains of staphylococci resistant to methicillin (MRSA) confirmed the applicability of the mecA-specific detection system. Total DNAs were extracted from five different wastewater treatment plants and used for direct TaqMan PCR detection of the resistance genes without prior cultivation. In municipal wastewater, the resistance gene vanA was detected in 21% of the samples, and ampC in 78%. The gene mecA was not found in municipal wastewater, but in two clinical wastewater samples.

Alaris AEP monitor's "Click Detection" does not help to detect inadvertent disconnection of headphones during anesthesia.

UNLABELLED: Auditory evoked potentials (AEP) can be suppressed by anesthetics dose dependently, but may fail to be registered because of the absence of adequate auditory stimuli. The Alaris AEP monitor includes the "Click Detection" (CD) (generating the message "NO AEP" or "LOW AEP") to detect the loss of auditory stimuli. We investigated the accuracy of the CD in 17 patients awake (AWAKE) and during anesthesia (ANESTHESIA) with accurately placed headphones (HP) and after disconnected HP (No HP) over 5 min each, respectively. Alaris AEP ARX index, CD, and Bispectral Index were recorded each minute. Changes were evaluated with the Friedman and Wilcoxon test. Sensitivity (SEN) and specificity (SPE) and receiver operating characteristic curve were analyzed for the accuracy of the CD. During AWAKE after disconnection of the HP, Alaris AEP ARX index decreased significantly (P < 0.05). The CD was able to detect No HP after 2 min with a SEN of 88% and a SPE of 97%. During ANESTHESIA, no changes were found after HP disconnection. CD detected No HP with a SEN of 100% and a SPE of 20%. The CD of the Alaris AEP monitor is not able to detect unnoticed disconnection of HP during ANESTHESIA. IMPLICATIONS: Signal transmission of auditory evoked potentials can be suppressed by anesthetics, but also by disconnection of headphones. In the present study, we demonstrate that even the Alaris AEP monitor with the very new feature "Click Detection" was not able to detect the loss of headphones during general anesthesia with propofol and remifentanil.

Narcotrend and Bispectral Index monitor are superior to classic electroencephalographic parameters for the assessment of anesthetic states during propofol-remifentanil anesthesia.

BACKGROUND: A new electroencephalogram monitor, the Narcotrend, was developed to measure anesthetic depth. The authors compared the Narcotrend, the Bispectral Index, and classic electroencephalographic and hemodynamic parameters during anesthesia with propofol and remifentanil. METHODS: The authors investigated 25 patients undergoing laminectomy at different anesthetic states: awake, steady state anesthesia, first reaction during emergence, and extubation. Narcotrend value; BIS; relative power (percent) in delta, theta, alpha, and beta; median frequency; spectral edge frequency; and hemodynamic parameters were recorded simultaneously. The ability of the classic and processed electroencephalographic and hemodynamic parameters to predict the clinically relevant anesthetic states of awake, steady state anesthesia, first reaction, and extubation was tested using prediction probability. RESULTS: Only the Narcotrend was able to differentiate between awake versus steady state anesthesia and steady state anesthesia versus first reaction/extubation with a prediction probability value of more than 0.90. CONCLUSIONS: Modern electroencephalographic parameters, especially Narcotrend, are more reliable indicators for the clinical assessment of anesthetic states than classic parameters.

ARX-derived auditory evoked potential index and bispectral index during the induction of anesthesia with propofol and remifentanil.

UNLABELLED: A new commercial auditory evoked potential (AEP) monitor (A-line AEP monitor) was developed to calculate an index (ARX AEP index; AAI) by automatically using the amplitudes and latencies of the AEP. We investigated 30 patients before spine surgery. AAI; bispectral index (BIS); relative (%) delta, theta, alpha, and beta; spectral edge frequency; median frequency; mean arterial blood pressure; heart rate; and oxygen saturation were obtained simultaneously during stepwise (1.0 micro g/mL) induction of target-controlled propofol concentration until 5.0 micro g/mL, followed by an infusion of 0.3 micro g. kg(-1). min(-1) of remifentanil. Every minute, the patients were asked to squeeze the observer's hand. Prediction probability (Pk), receiver operating characteristic, and logistic regression were used to calculate the probability to predict the conditions AWAKE, UNCONSCIOUSNESS (first loss of hand squeeze), and steady-state ANESTHESIA (5.0 micro g/mL of propofol and 0.3 micro g. kg(-1). min(-1) of remifentanil). Although a statistically significant difference among the conditions was observed for AAI, BIS, mean arterial blood pressure, median frequency, and %alpha, only AAI and BIS were able to distinguish UNCONSCIOUSNESS versus AWAKE and ANESTHESIA versus AWAKE with better than Pk = 0.90. The modern electroencephalographic variables AAI and BIS were superior to the classic electroencephalographic and hemodynamic variables to distinguish the observed anesthetic conditions. IMPLICATIONS: The modern electroencephalographic ARX-derived auditory evoked potential index and the bispectral index were superior to the classic electroencephalographic and hemodynamic variables for predicting anesthetic conditions. Variables derived from the auditory evoked potential did not provide an advantage over variables derived from spontaneous electroencephalogram.