The major finding of this study was that the duration of BIS values below 40 coupled with MAP less than 50 mmHg was associated with 90-day postoperative mortality. This suggests that excessive anesthetic-induced brain suppression as well as intraoperative hypotension may be associated with adverse postoperative outcome.
This study found that the ‘simultaneous double low’, the cumulative time of BIS values less than 40 coupled with MAP less than 50 mmHg was associated with 90-day postoperative mortality. In contrast, the cumulative durations of BIS values less than 40, BIS values less than 20, and EEG suppression alone were not related to postoperative mortality, similar to several previous reports.(7, 12) These findings may imply that it is not possible to predict mortality by excessive suppression alone, but only with combined hypotension.
On the other hand, the simultaneous double low of BIS values less than 40 and MAP less than 50 mmHg was not associated with postoperative 180-day mortality. This finding suggests that intraoperative low BIS values and blood pressure seem to be related to early-to-intermediate postoperative mortality and not to intermediate-to-long term mortality. The sequelae of intraoperative events and excessive anesthesia can lead to early postoperative complications which is associated with early-to-intermediate mortality, but the effect seems to be time-limited.
In this study, mean propofol concentrations were not statistically different between patients with or without double-low among TIVA cases. Therefore, patients who presented double-low may have had higher anesthetic vulnerability, which means that some patients are prone to show lower BIS values and hypotension in similar anesthetic dosage, followed by postoperative adverse outcomes. On the other hand, in inhalational anesthesia, mean MAC of volatile anesthetics was higher in the patients with double-low. In this respect, excessive anesthesia also can be a cause of double-low and, furthermore, postoperative mortality. Further research is needed to investigate the difference in anesthetic vulnerability according to the type of anesthesia. Nevertheless, BIS monitoring and titration of anesthetics can help avoid unnecessarily deep anesthesia and possible neurotoxic effects in vulnerable patients,(17) yet there is still a lack of evidence by prospective studies(14) whether avoiding ‘double low’ state can improve postoperative outcomes.
The Vital Recorder program, which was used to collect BIS values, suppression ratios and MAP data in this study, is an automatic recording device for obtaining high-resolution time-synchronized physiological data from multiple anesthesia devices.(18) With this software we could obtain stored digitalized data for every patient, as well as accurately compute the independent variables related to BIS and MAP. Furthermore, intraoperative target site propofol concentrations in TIVA and MAC of volatile agents in inhalational anesthesia were recorded in real time.
This study derived relationship between the cumulative duration of concurrent double-low and postoperative mortality, especially focusing on the abdominal surgeries including gastrointestinal tract, liver, biliary tract, and pancreas surgeries. Other previous studies revealed comparable results on influence of low BIS and hypotension in other types of surgeries,(13, 14) and this study can support the results so far in respect of major abdominal surgery. Meanwhile, the cutoff value of MAP was 50 mmHg in this study according to several definitions of clinically significant hypotension.(19, 20) Although it would be less conservative than the cutoff value of 75 mmHg, we tried to investigate narrower sense of definition of double-low.
This study had several limitations. First, the incidence of postoperative mortality was relatively smaller than that in previous reports.(21) For a more accurate statistical analysis, a larger number of cases would be needed. Second, this study has limitation from the design of retrospective study. Data can be incomplete. Nevertheless, all intraoperative data were completely obtained using the ‘Vital Recorder program. Third, we included only patients receiving major abdominal surgeries to decrease other bias originated from different surgery and population. However, this may be another limitation for generalization of our results.