Background Awareness during anesthesia is a serious complication with potential long-term psychological consequences. Use of the bispectral index (BIS), developed from a processed electroencephalogram, has been reported to decrease the incidence of anesthesia awareness when the BIS value is maintained below 60. In this trial, we sought to determine whether a BIS-based protocol is better than a protocol based on a measurement of end-tidal anesthetic gas (ETAG) for decreasing anesthesia awareness in patients at high risk for this complication. Methods We randomly assigned 2000 patients to BIS-guided anesthesia (target BIS range, 40 to 60) or ETAG-guided anesthesia (target ETAG range, 0.7 to 1.3 minimum alveolar concentration [MAC]). Postoperatively, patients were assessed for anesthesia awareness at three intervals (0 to 24 hours, 24 to 72 hours, and 30 days after extubation). Results We assessed 967 and 974 patients from the BIS and ETAG groups, respectively. Two cases of definite anesthesia awareness occurred in each group (absolute difference, 0%; 95% confidence interval [CI], −0.56 to 0.57%). The BIS value was greater than 60 in one case of definite anesthesia awareness, and the ETAG concentrations were less than 0.7 MAC in three cases. For all patients, the mean (±SD) time-averaged ETAG concentration was 0.81±0.25 MAC in the BIS group and 0.82±0.23 MAC in the ETAG group (P = 0.10; 95% CI for the difference between the BIS and ETAG groups, −0.04 to 0.01 MAC). Conclusions We did not reproduce the results of previous studies that reported a lower incidence of anesthesia awareness with BIS monitoring, and the use of the BIS protocol was not associated with reduced administration of volatile anesthetic gases. Anesthesia awareness occurred even when BIS values and ETAG concentrations were within the target ranges. Our findings do not support routine BIS monitoring as part of standard practice. (ClinicalTrials.gov number, NCT00281489.)

https://www.nejm.org/doi/pdf/10.1056/NEJMoa0707361

Anesthesia Awareness and the Bispectral Index

Awareness with recall after general anesthesia is an infrequent, but well described, phenomenon that may result in posttraumatic stress disorder. There are no recent data on the incidence of this complication in the United States. We, therefore, undertook a prospective study to determine the incidence of awareness with recall during general anesthesia in the United States. This is a prospective, nonrandomized descriptive cohort study that was conducted at seven academic medical centers in the United States. Patients scheduled for surgery under general anesthesia were interviewed in the postoperative recovery room and at least a week after anesthesia and surgery by using a structured interview. Data from 19,575 patients are presented. A total of 25 awareness cases were identified (0.13% incidence). These occurred at a rate of 1-2 cases per 1000 patients at each site. Awareness was associated with increased ASA physical status (odds ratio, 2.41; 95% confidence interval, 1.04-5.60 for ASA status III-V compared with ASA status I-II). Age and sex did not influence the incidence of awareness. There were 46 additional cases (0.24%) of possible awareness and 1183 cases (6.04%) of possible intraoperative dreaming. The incidence of awareness during general anesthesia with recall in the United States is comparable to that described in other countries. Assuming that approximately 20 million anesthetics are administered in the United States annually, we can expect approximately 26,000 cases to occur each year.

The incidence of awareness during anesthesia: a multicenter United States study.

https://www.thelancet.com/pdfs/journals/lancet/PIIS0140-6736(99)11010-9.pdf

Awareness during anaesthesia: a prospective case study

The set of guidelines for good clinical research practice (GCRP) in pharmacodynamic studies of neuromuscular blocking agents, which was developed following an international consensus conference in Copenhagen, has been revised and updated following the second consensus conference in Stockholm in 2005. It is hoped that these guidelines will continue to help researchers in the field and assist the pharmaceutical industry and equipment manufacturers in enhancing the standards of the studies they sponsor.

https://onlinelibrary.wiley.com/doi/pdf/10.1111/j.1399-6576.2007.01352.x

Good clinical research practice in pharmacodynamic studies of neuromuscular blocking agents II: the Stockholm revision.

Based on an international consensus conference held in Copenhagen in the autumn of 1994, a set of guidelines for Good Clinical Research Practice (GCRP) in pharmacodynamic studies of neuromuscular blocking agents are presented. The guidelines are intended to be a help for people working in this research field, and it is hoped that the guidelines will assist researchers, editors, and drug companies to enhance the quality of their pharmacodynamic studies of neuromuscular blocking agents.

Good Clinical Research Practice (GCRP) in pharmacodynamic studies of neuromuscular blocking agents

SUMMARY An investigation is described into the problems of recall and dreaming under light anaesthesia with nitrous oxide, muscle relaxation being provided by tubocurarine, and the anaesthetic technique being, as far as possible, standardized. Tape-recorded music of two types was used to test the patient's ability to hear and, in addition, the nature and quality of dreams was investigated. There was no evidence that patients were able to hear the tape-recordings and there was no evidence of "awareness" during the operative procedure. Dreaming occurred in 44 per cent of the patients and details of the dreams were recalled in some two-thirds of these. Hypocapnia did not protect against dreaming. Patients who showed marked movement during the operative procedure were more liable to dream than those who did not; the significance of this movement is discussed. In this (unpremedicated) group of patients nearly half described waiting for surgery as the most unpleasant feature of their surgical experience, and postoperative pain was the major complaint in a further 20 per cent. The third commonest of the major complaints was related to requests to lift the head, etc., when unable to do so in the time immediately after operation, and this finding would seem to have some minor practical significance. Unpleasant dreams were the fourth commonest major complaint.

A simple study of awareness and dreaming during anaesthesia

SUMMARY Study of the literature on the physiology of neuromuscular transmission suggested two new methods of assessing the degree of neuromuscular block in the human subject. These were, first, a comparison of the height of the recorded twitch tensions developed in response to repeated single stimuli applied at differing frequencies and, second, examination of the extent of reduction in amplitude of twitch tensions developed in response to a short train of four stimuli. In assessing the first method the use of three frequencies of stimulation was tried (i.e., 0.1 Hz (c.p.s.), 0.3 Hz and 1.0 Hz). It was found that as the frequency of stimulation was increased there was reduction in the amplitude of the recorded twitch response in curarized subjects, and that this reduction appeared to depend on the degree of curarization. In assessing the second method a short train of four stimuli at 2 Hz was used, and it was found that there was a progressive fade of successive recorded mechanical twitch responses in curarized subjects which again appeared to depend on the degree of curarization. It is suggested that the amplitude of the twitch response at a higher frequency expressed as a percentage of that at the slower rate, and the last response of the train of four expressed as a percentage of the first may be useful in measuring degree of neuromuscular block in man.

Stimulus frequency in the detection of neuromuscular block in humans

/pdf/a-simple-study-of-awareness-and-dreaming-during-anaesthesia-28vtyiwg17.pdf

An attempt to estimate residual neuromuscular blockade after the administration of anti-depolarizing relaxants to anaesthetized patients is described. A train of four supra-maximal nerve stimuli was applied to the ulnar nerve and the twitch response (mechanical or electrical) was recorded. The frequency of the train used was 2–2.4 Hz with an interval of 10 seconds between the trains. Clinical recovery from the relaxant was assessed by the ability to lift the head. The ratio of the height of the fourth response of the train to that of the first (ratio (c)) gave a good indication of the degree of residual neuromuscular block as indicated by this simple clinical test. As ratio (c) increased muscle power improved. Obvious muscle weakness was associated with values of ratio (c) of less than 0.6.

Quantitative assessment of residual antidepolarizing block (part ii)

Atracurium was given to 26 patients who had no renal function; in 21 of these neuromuscular block was monitored using the train-of-four stimuli. The results are compared with those obtained from normal patients presented for surgery. Unlike the non-depolarizing muscle relaxants currently in common use, it was possible to continue giving incremental doses of atracunum to the anephric patients without there being evidence of cumulation. Even when the total dose used (over a period of up to 2.5 h) was in the order of seven to eight times that previously described as the minimum required for endotracheal intubation (2.3mg kg−1 as opposed to 0.3 mg kg−1), there was no evidence of residual curarization. This finding would seem to be compatible with what is known of the pharmacology of the drug. No adverse cardiovascular effects were demonstrated. It is concluded that atracurium may be especially valuable in patients with no renal function.

J.E. Utting

Papers

A simple study of awareness and dreaming during anaesthesia

Stimulus frequency in the detection of neuromuscular block in humans

A simple study of awareness and dreaming during anaesthesia

Quantitative assessment of residual antidepolarizing block (part ii)

Use of atracurium in patients with no renal function