This Article Abstract Full Text (PDF) Alert me when this article is cited Alert me if a correction is posted Services Email this article to a colleague Similar articles in this journal Similar articles in Web of Science Similar articles in PubMed Alert me to new issues of the journal Download to citation manager Request Permissions Citing Articles Citing Articles via Google Scholar Google Scholar Articles by Mayer, J. Articles by Suttner, S. W. Search for Related Content PubMed PubMed Citation Articles by Mayer, J. Articles by Suttner, S. W.

---

TECHNOLOGY, COMPUTING, AND SIMULATION

Bispectral Index-Guided General Anesthesia in Combination with Thoracic Epidural Analgesia Reduces Recovery Time in Fast-Track Colon Surgery

Jochen Mayer, MD^*, Joachim Boldt, MD, PhD^*, Alexander Schellhaaß, MD^*, Björn Hiller, MD, and Stefan W. Suttner, MD^*

From the *Department of Anesthesiology and Intensive Care Medicine, Klinikum Ludwigshafen, Germany and Department of General Surgery, Klinikum Ludwigshafen, Germany.

Address correspondence to: Dr. Jochen Mayer, Department of Anesthesiology and Intensive Care Medicine, Klinikum Ludwigshafen, Bremserstr. 79, 67063 Ludwigshafen, Germany. Address e-mail to j-mayer{at}gmx.de.

	Abstract

Top Abstract Introduction METHODS RESULTS DISCUSSION REFERENCES

 
BACKGROUND: The impact of bispectral index (BIS)-guided general anesthesia on recovery from general anesthesia has been evaluated in different patient populations. The benefit of using BIS has been inconsistent. We designed this study to examine the value of BIS-guided anesthesia in a fast-track setting where the goal is rapid recovery.

METHODS: Forty-four patients undergoing open colon resection were randomly assigned to receive either BIS-guided (BIS group, n = 22) or clinically guided (standard care group, n = 22) total IV anesthesia with propofol after placing a thoracic epidural catheter. Duration of postanesthesia care unit stay, time to tracheal extubation, direct drug cost, the incidence of hemodynamic abnormalities, ability of ambulation on the day of surgery, and patient satisfaction with anesthetic management were assessed.

RESULTS: In the BIS-guided group, tracheal extubation was achieved significantly earlier (7.6 vs. 15.4 min, P < 0.01) and the postanesthesia care unit stay was significantly shorter (51 vs. 85 min, P < 0.01). Total anesthetic drug cost was reduced by 23% and the incidence of hypotension requiring treatment was significantly lower in the BIS group. Early ambulation, patient satisfaction, and incidence of adverse events were not significantly different between the groups.

CONCLUSIONS: BIS-guided IV anesthesia in combination with thoracic epidural analgesia facilitates rapid recovery and reduces the overall cost of care in patients undergoing fast-track colon surgery.

	Introduction

Top Abstract Introduction METHODS RESULTS DISCUSSION REFERENCES

 
It has been shown that a multimodal perioperative "fast-track" technique can reduce postoperative morbidity (1) and facilitate earlier hospital discharge, based upon the same discharge criteria as with traditional care (2). Optimized fluid and pain management, less invasive surgical techniques, early postoperative oral nutrition, and an increased emphasis on physical rehabilitation result in a reduced stress response and less discomfort for patients, leading to accelerated recovery. Intra- and postoperative anesthetic management with short-acting anesthetics in combination with thoracic epidural analgesia is one approach to facilitate early recovery and mobilization.

The bispectral index (BIS) is a dimensionless number between 0 and 100, calculated from the electroencephalogram signal, which has been proven to correlate well with the hypnotic state of the patient during both inhaled and IV anesthesia (3). The recommended target range for the BIS value during surgical anesthesia is between 40 and 60 (4). The BIS monitor is used to reduce the risk of intraoperative awareness (5) and to guide administration of anesthetics to prevent unnecessarily deep anesthesia and the resulting prolonged recovery time. Data about improving the recovery process by BIS-titrated anesthetic agents have been inconsistent. The recovery process appears to be dependant on factors such as age, gender, ASA physical status, and duration of anesthesia (6,7). The objective of this study was to assess the effects of BIS-guided general anesthesia in combination with thoracic epidural analgesia on recovery times and early mobilization in patients undergoing elective fast-track colon surgery. Our hypothesis was that immediate postoperative recovery would be faster, and more patients could be mobilized earlier, in the BIS-controlled group.

	METHODS

Top Abstract Introduction METHODS RESULTS DISCUSSION REFERENCES

 
Forty-four patients of ASA physical status I–III aged 48 to 82 yr scheduled for elective fast-track colon surgery (open left or right hemicolectomy, sigmoid resection) were studied after IRB approval and obtaining written informed consent. Patients with a history of chronic brain disease (epilepsy, Alzheimer’s dementia, previous brain resection), heavy alcohol intake, benzodiazepine or opioid abuse, liver disease, psychiatric disorders or impossibility of establishing epidural analgesia (impaired coagulation, previous spine surgery in the area of the puncture, rejection of the patients) were excluded.

All patients received midazolam 0.1 mg/kg orally 60 min before induction of anesthesia. A thoracic epidural catheter was inserted and advanced 3–5 cm into the epidural space using a midline approach between T7 and T9. Ropivacaine 0.75% 1 mg/kg and sufentanil 0.25 µg/kg were administered after a test dose of 3 mL of 1% prilocaine. The level of somatosensory blockade was determined by touching the skin with ice and performing the pinprick test.

Patients were randomly assigned using a closed envelope system to receive either BIS-controlled (BIS XP-module, Datex Ohmeda, Freiburg, Germany, software version 4.0) anesthesia (BIS group) or clinically guided (standard care group) total IV anesthesia with propofol as the hypnotic drug. In the BIS group, the BIS electrodes (Quatro sensor, Aspect Medical, Newton, MA) were placed on the forehead of the dominant hemisphere according to the guidelines of the manufacturer. Anesthesia was induced with propofol 2 mg/kg, fentanyl 1–2 µg/kg, and cisatracurium 0.15 mg/kg. In the BIS group, hypnosis was maintained using a continuous propofol infusion of 5 mg/kg/h with a syringe pump (Perfusor, B.Braun, Melsungen, Germany), adjusted in steps of 0.5 mg/kg/h to maintain a BIS value between 40 and 50 until commencement of skin closure. The BIS values were displayed continuously to the anesthesia provider (Datex S/5, Datex Ohmeda, Freiburg, Germany) and digitally recorded every 5 min along with other vital data using custom software (NarkoData, Imeso, Hüttenberg, Germany). The time-averaged mean BIS value was calculated using the automatically recorded data and the signal quality index was documented. In the standard care group, the same infusion device and starting dose were used to maintain hypnosis as in the BIS group, but titration of propfol was controlled in steps of 0.5 mg/kg/h by means of clinical data (mean arterial blood pressure (MAP), heart rate, appearance of tears, etc.). Both groups received an additional dose of ropivacaine 0.75% (1 mg/kg) and sufentanil (0.25 µg/kg) via the epidural catheter 20 min before skin incision. For further intraoperative pain relief, a Graseby 9500 epidural infusion pump (Smith Medical, Watford, UK) was used to administer 4 mL/h of a mixture of ropivacaine 0.2% and sufentanil 1 µg/mL. Additional boluses of 6 mL of the epidural infusion mixture could be given according to the patients’ needs. The thoracic epidural catheter was considered effective for surgical pain relief, if patients did not need an additional fentanyl bolus for abdominal laparotomy. Neuromuscular blockade was guided by train-of-four monitoring and cisatracurium (2–4 mg) was given when the applied current to the radial nerve of 50 mA resulted in one or more twitches of the thumb. In both groups, ventilation was controlled to maintain normocapnia (expiratory Pco₂ 32–38 mm Hg) using a constant fresh gas flow of 1 L/min (50% air in oxygen) in a semiclosed circle system. Standard monitoring included electrocardiogram, noninvasive MAP, pulse oximetry, temperature, and inspiratory and expiratory gas concentrations. No central venous lines and invasive MAP measurements were established.

To maintain intraoperative normothermia, the operating room temperature was increased to 25°C, and the patients were provided with warm air blankets to cover the lower extremity.

A baseline noninvasive MAP was obtained on the preoperative day, averaged over four defined measuring times (Table 1). Perioperative hypotension was defined as a MAP <60 mm Hg and was treated with 500 mL hydroxyethylstarch 6% (Voluven®, Fresenius Kabi, Germany), followed by bolus doses of norepinephrine or a continuous infusion of norepinephrine in both groups as needed. If MAP increased to >100 mm Hg in the BIS group despite adequate hypnosis, an additional 6 mL bolus of the ropivacaine/ sufentanil mixture was given via the epidural catheter. A small amount of fentanyl (0.5 µg/kg) was administered simultaneously to bridge the time the epidural medication needed to take effect. In the standard care group, the treatment of an increased MAP (>100 mm Hg) consisted of an increase of the propofol infusion by 0.5 mg/kg/h. In case of hypertension caused by insufficient analgesia, an increased propofol infusion rate of 0.5 mg/kg/h is not likely to sufficiently control hypertension. As in the BIS group, a small fentanyl bolus (0.5 µg/kg) was given in this case along with an additional epidural bolus of 6 mL ropivacaine/sufentanil. Fluid administration was restricted to 10 mL/kg/h (5 mL/kg/h for crystalloids and 5 mL/kg/h for colloids) in both groups. Blood loss was substituted by colloid solution and a hemoglobin value below 8 mg/dL was considered as a trigger for transfusion of packed red blood cells.

At the commencement of skin closure, propofol administration was stopped and recovery of neuromuscular function was confirmed using the train-of-four method. The time to tracheal extubation was calculated from termination of the propofol infusion until removal of the endotracheal tube. All patients were transferred to the postanesthesia care unit (PACU) and modified Aldrete scores (8) were obtained on arrival. Adverse events (nausea, vomiting, shivering, desaturation) were recorded after tracheal extubation and during PACU stay. Epidural analgesia was continued using the patient-controlled analgesia mode of the epidural infusion device during emergence and PACU stay until removal of the catheter at postoperative day two. Pain was assessed in the postoperative period using a visual analog scale (VAS, vertical numerical scale of 0–10 marked off in units of 1 point; 0 score indicating no pain and 10 points indicating the worst possible pain). Morphine and/or nonsteroidal antiinflammatory drugs (paracetamol or diclofenac) were provided as rescue medication in case of insufficient epidural analgesia or accidental catheter removal. Patients were considered ready for discharge from PACU with an Aldrete score 9 and a VAS 3 and if there was no evidence of postoperative nausea and vomiting, surgical complications such as bleeding or motor blockade due to epidural analgesia. The patients were assessed every 10 min by a blinded study nurse, and the time they met the criteria for discharge was recorded. On the surgical ward, mobilization of the patients was started 6 h after discharge from the PACU.

All patients were routinely visited once a day until discharge and were interviewed to determine the time of the first defecation and pain scores were recorded by a study nurse blinded to the patients’ group assignment. Satisfaction with the anesthetic management was also recorded using a VAS (0 score indicating not satisfied and 10 points indicating complete satisfaction). In both groups, experienced anesthesiologists, blinded to the study design, cared for patients. To avoid learning contamination bias, we had a pool of seven anesthesiologists for each group. All data were collected by a study nurse blinded to group assignment, data were not collected automatically.

The primary outcome variable was the duration of PACU stay. Secondary outcome variables were the ability of ambulation on the day of surgery, incidence of hemodynamic abnormalities (hypotension, hypertension), time to extubation, direct drug cost, time to defecation, and patient satisfaction.

The number of patients required in each group was determined before the study by a power calculation based on the results of a pilot study of nine patients. The minimum clinically important difference we wished to detect was a 25% decrease in the primary end-point duration of PACU stay. We estimated that the standard deviation (sd) of PACU stay values would be up to 30 min. The error was set at 0.05 (two-sided) and type II error at 0.2. Based on these assumptions, 17 patients per group were required. To compensate for possible dropouts, we decided to include 22 patients per group.

Ordinal data (demographic data, measured time intervals) are expressed as mean ± sd and were analyzed using the Student’s t-test. Normal distribution was determined using the ² test. Nonparametric data including pain scores and the incidence of adverse events were compared using the Wilcoxon’s ranked sum test. The Fisher’s exact test was used to compare proportions. P values <0.05 were considered significant.

	RESULTS

Top Abstract Introduction METHODS RESULTS DISCUSSION REFERENCES

 
Both groups were comparable with respect to age, gender, body-mass index, consumption of fentanyl, and blood loss. Duration of anesthesia and surgery and crystalloid fluid administration also did not differ between the groups (Table 1). Sufficient sensory epidural blockade (T9) was achieved in all patients and extension was comparable between the groups (Table 1). No patient had to be excluded due to insufficient intraoperative epidural analgesia. Consumption of propofol was significantly lower in the BIS group (4.7 vs. 5.88 mg/kg/h, P < 0.01). Time to tracheal extubation was significantly shorter in patients with BIS-guided anesthesia (Table 2). The modified Aldrete score on arrival in PACU was significantly lower in the standard care group (Table 2). Patients receiving BIS-guided anesthesia were discharged from the PACU sooner (51 vs. 85 min P < 0.001), mainly because of higher Aldrete values for consciousness and circulation. Episodes of hypotension requiring treatment were seen more often in the standard care group (Table 3). Direct drug cost was reduced by 23% (P < 0.01) in the BIS group. No differences were found between the study groups with respect to pain, nausea, vomiting, shivering, desaturation, administered doses of epidural medication, and the need for rescue medication.

On follow-up, 20 of 22 (90%) patients in the BIS-group were able to get out of bed on the day of surgery compared to 19 of 22 (86%) patients in the standard care group (P = 1.0). Time to first defecation and patient satisfaction were not significantly different between the two groups (Table 3).

	DISCUSSION

Top Abstract Introduction METHODS RESULTS DISCUSSION REFERENCES

 
This study examined the impact of BIS monitoring on several indices of recovery using patients undergoing colon surgery and managed with a fast-track anesthetic technique consisting of thoracic epidural analgesia and IV propofol. The results indicate that BIS monitoring reduced the time to tracheal extubation, the time to PACU discharge and the cost of IV drugs administered.

BIS monitoring has been proven to be a valuable tool to measure anesthetic depth (9), and therefore provides assistance in determining adequate hypnotic doses of propofol. Myles et al. (5) showed in a large trial that BIS monitoring markedly reduces the risk of intraoperative awareness. The literature of improved emergence and shorter PACU stays with BIS-guided anesthesia however is far from uniform. Some studies suggest that BIS-controlled anesthesia leads to faster emergence and improved recovery (4,5,7,10); others were not able to show differences in the patients’ recovery profiles after general anesthesia (14–16) (11–13). There might be a variety of reasons for this inconsistency. Required propofol doses are influenced by gender: women seem to be less sensitive to the hypnotic effect of propofol than men and experience faster emergence (6). For this reason, we sought a balanced male–female ratio to avoid bias in our study.

Apart from the aforementioned characteristics, there is also evidence that thoracic epidural analgesia decreases the requirement of propofol. It has been found that both the induction dose and maintenance dose are lower with effective epidural analgesia (14). Accordingly, emergence and duration of PACU stay is most likely influenced. Not all studies dealing with emergence after BIS-guided anesthesia used epidural analgesia, and hence results might not be comparable. In our study, the initial bolus of epidural medication was evenly divided to attenuate hypotension after epidural injection. Another reason which might explain different findings is the varying duration of anesthesia. The context-sensitive half-life of propofol increases with time (15). Significant savings of propofol might therefore be achieved with BIS-guided anesthesia in long lasting anesthesia.

BIS-measurements are susceptible to a range of sources of error. In a recent review article on errors with BIS (16), electromyography artifact signals in patients undergoing general anesthesia without neuromuscular blocking drugs or air-warming blankets, placed close to a patient’s forehead, were reported to increase the calculated BIS-value without affecting the signal quality indicator. This issue was incorporated in our study protocol. In particular, use of systemic opioids was avoided, air-warming blankets were placed over the lower extremity, no nitrous oxide but neuromuscular blocking agents were used, and no BIS-values were recorded during electrocautery.

Cost analysis of anesthetic techniques is necessary in today’s economic climate. With the use of BIS-monitoring, the reduced propofol consumption (wastage included) was able to reduce total drug cost by 23%, which justifies the cost of the BIS-sensor in our study population with an average anesthesia time of 249 ± 79 min. The reduced costs of faster tracheal extubation and subsequent savings of operating theater time and a shorter PACU stay in the BIS-guided group have not been considered in this calculation.

We were not able to show significant differences in the time of patient mobilization. Although lower quantities of propofol consumption and less PACU time were observed in the BIS-group, the key factor for early mobilization is most probably sufficient analgesia provided by epidural catheterization, and not a lower quantity of propofol administration attenuating after-effects of anesthesia. As both groups received almost the same doses of opioids, and identical surgical techniques were applied, there was no discrepancy in the time to first defecation.

In conclusion, BIS-guided anesthesia in a fast-track setting in combination with thoracic epidural analgesia results in reduced IV drug administration, less intraoperative hypotension, faster emergence from anesthesia and shorter duration of cost-intensive PACU-stay. Anesthetic management is a major contributing factor to the success of a rapid and patient-friendly procedure. Differences in the long-term outcome and a concise cost analysis are subjects for further investigation.

	Footnotes

 
Accepted for publication January 15, 2007.

	REFERENCES

Top Abstract Introduction METHODS RESULTS DISCUSSION REFERENCES

 

1. Kehlet H, Wilmore DW. Fast-track surgery. Br J Surg 2005; 92:3–4.[Web of Science][Medline]
2. Kehlet H, Dahl JB. Anaesthesia, surgery, and challenges in postoperative recovery. Lancet 2003;362:1921–8.[Web of Science][Medline]
3. Glass PSA, Bloom M, Kearse LAJ, et al. Bispectral analysis measures sedation and memory effects of propofol, midazolam, isoflurane, and alfentanil in healthy volunteers. Anesthesiology 1997;86:836–47.[Web of Science][Medline]
4. Gan TJ, Glass PS, Windsor A, et al. Bispectral index monitoring allows faster emergence and improved recovery from propofol, alfentanil, and nitrous oxide anesthesia. Anesthesiology 1997; 87:808–15.[Web of Science][Medline]
5. Myles PS, Leslie K, McNeil J, et al. Bispectral index monitoring to prevent awareness during anesthesia: the B-Aware randomised controlled trial. Lancet 2004;363:1757–63.[Web of Science][Medline]
6. Buchanan F, Myles PS, Leslie K, et al. Gender and recovery after general anesthesia combined with neuromuscular blocking drugs. Anesth Analg 2006;102:291–7.[Abstract/Free Full Text]
7. Leslie K, Myles PS, Forbes A, et al. Recovery from bispectral index-guided anesthesia in a large randomized controlled trial of patients at high risk of awareness. Anaesth Intensive Care 2005;33:443–51.[Web of Science][Medline]
8. Aldrete JA. The postanesthesia recovery score revisited. J Clin Anesth 1995;7:89–91.[Web of Science][Medline]
9. Drummond JC. Monitoring depth of anesthesia: with emphasis on the application of the bispectral index and the middle latency auditory evoked response to the prevention of recall. Anesthesiology 2000;93:876–82.[Web of Science][Medline]
10. Song D, Joshi GP, White PF. Titration of volatile anesthetics using bispectral index facilitates recovery after ambulatory anesthesia. Anesthesiology 1997;87:842–8.[Web of Science][Medline]
11. Zohar E, Luban I, White PF, Ramati E, Shabat S, Fredman B. Bispectral index monitoring does not improve early recovery of geriatric outpatients undergoing brief surgical procedures. Can J Anesth 2006;53:20–25.[Web of Science][Medline]
12. Ahmad S, Yilmaz M, Marcus RJ, Glisson S, Kinsella A. Impact of bispectral index monitorting on fast tracking of gynecologic patients undergoing laparoscopic surgery. Anesthesiology 2003;98:849–52.[Web of Science][Medline]
13. Bruhn J, Kreuer S, Bischoff P, Kessler P, Schmidt GN, Grzesiak A, Wilhelm W. Bispectral index and A-line AAI index as guidance for desflurane-remifentanil anaesthesia compared with a standard practice group: a multicentre study. Br J Anaesth 2005;94:63–9.[Abstract/Free Full Text]
14. Agarwal A, Pandey R, Dhiraaj S, et al. The effect of epidural bupivacaine on induction and maintenance doses of propofol (evaluated by bispectral index) and maintenance doses of fentanyl and vecuronium. Anesth Analg 2004;99:1684–8.[Abstract/Free Full Text]
15. Hughes MA, Glass PSA, Jacobs JR. Context sensitive half-time in multicompartment pharmacokinetic models for intravenous anesthetic drugs. Anesthesiology 1992;76:332–41.
16. Dahaba AA. Different conditions that could result in bispectral index indicating an incorrect hypnotic state. Anesth Analg 2005;101:765–73.[Abstract/Free Full Text]

This Article Abstract Full Text (PDF) Alert me when this article is cited Alert me if a correction is posted Services Email this article to a colleague Similar articles in this journal Similar articles in Web of Science Similar articles in PubMed Alert me to new issues of the journal Download to citation manager Request Permissions Citing Articles Citing Articles via Google Scholar Google Scholar Articles by Mayer, J. Articles by Suttner, S. W. Search for Related Content PubMed PubMed Citation Articles by Mayer, J. Articles by Suttner, S. W.