Isoflurane and sevoflurane decrease entropy indices more than halothane at equal MAC values

Recently, bispectral index (BIS) values were demonstrated to be different for various anesthetics as a result of differential effects on electroencephalographic (EEG) signals. Entropy is similar to the BIS monitor, as both process raw EEG to derive a number. We hypothesized that entropy may also be anesthetic agent-specific. Thirty adult patients undergoing spinal surgery were randomized to receive halothane, isoflurane, or sevoflurane. Entropy indices were recorded at various minimum alveolar concentration (MAC) values—0.5, 0.75, 1.0 and 1.5—both during wash-in and wash-out of the agent. Heart rate (HR), mean arterial blood pressure (MAP), response entropy (RE), and state entropy (SE) were noted. Statistical analysis was done using a one-way analysis-ofvariance test. P values less than 0.05 were considered significant. Ten patients in each group completed the study. The demographics and baseline values of HR, MAP, RE, and SE were comparable in all three groups. During the study period, for a given MAC value, both RE and SE remained low in the isoflurane and sevoflurane groups compared to the halothane group. For a given MAC, the RE and SE were comparable during wash-in and wash-out phases. Halothane produced higher entropy values as compared to isoflurane and sevoflurane at equivalent MAC levels.     

Sevoflurane causes more postoperative agitation in children than does halothane

BACKGROUND: An agitated recovery may occur after inhalation anesthesia. The aim of the present study was to assess the recovery quality after mask anesthesia with either halothane or sevoflurane in children. METHODS: Sixty-two children, 8 months to 18 years of age, scheduled for minor surgery, were randomly assigned to receive either halothane or sevoflurane. The patients were premedicated with midazolam and anesthesia was induced i.v. with propofol or by inhalation and maintained with halothane or sevoflurane in N2O/O2 via face mask. Recovery was assessed by a "blinded" observer using a postanesthetic recovery score. Agitation and pain were judged using a visual analog scale. The incidence of vomiting was noted. The day after anesthesia older children and parents of younger children were interviewed about their experience of the anesthesia and recovery period. RESULTS: There were no differences between groups in respect of age, weight, length, or duration of surgery or inhalational gas exposure. Median time from end of administration of inhalational agent to spontaneous eye opening was less after sevoflurane (25 min) than after halothane (48 min), (P < 0.01). Likewise, recovery was faster after sevoflurane anesthesia (P < 0.05). Agitation, but not pain, occurred more frequently after sevoflurane than after halothane (P < 0.05) and agitation was significantly more common in younger children. There was no difference in duration of hospital stay between day-care patients in the two groups. CONCLUSION: Early postanesthetic agitation and recovery was faster after mask anesthesia with sevoflurane than after halothane. There was a higher incidence of agitation in younger children, without correlation to pain.     

Sudden increases and decreases in bispectral index values more than 30 within 1 minute during general anesthesia

We described, in a 40-year-old man, sudden and unexpected increases in bispectral index values during the general anesthesia with total intravenous anesthesia using propofol in a dental surgery. The patient was administered continuous infusion of propofol and remifentanil, and intermittent supplementation of fentanyl. Immediately after the beginning of surgery, the bispectral index value increased abruptly to 90; whereas, heart rate and non-invasive blood pressure were unchanged and no physiological finding was observed. Approximately 25 min later, the value decreased to below 40 without any modification of anesthesia. The extent of unanticipated increase might be compatible with the duration of surgical procedure using dental air turbine. Therefore, the noise from surgical device might induce unpredictable change in bispectral index values.     

Verapamil decreases MAC for halothane in dogs

Verapamil hydrochloride is a calcium entry blocking drug that is being prescribed with increasing frequency for cardiovascular disorders in the perioperative setting. Verapamil's calcium channel blocking effect is not selective, because it also exerts activity on the sodium channel. Because of the well-described effects of sodium channel blockers on anesthetic requirements, the authors studied the MAC for halothane in dogs before and after a therapeutic dose of verapamil 0.5 mg . kg-1. There was a 25% reduction in halothane MAC from 0.97-0.72% (P less than 0.01) when a therapeutic plasma level of verapamil (64 ng . ml-1) was present. Anesthetic requirements for halothane are reduced by dl-verapamil possibly on the basis of its local anesthetic-like sodium channel blocking properties. Adjustments in anesthetic dosage may be necessary in patients receiving verapamil.     

Equi-MAC concentrations of halothane and isoflurane do not produce similar bispectral index values

Minimum alveolar concentration (MAC) has been traditionally used to measure the potency of an inhalational anesthetic agent. Recently, bispectral index (BIS) derived from the frontal cortical electroencephalogram has been used frequently for quantifying the hypnotic component of anesthesia. The present study was designed to examine the BIS values produced by equi-MAC concentrations of halothane and isoflurane. In 34 patients undergoing spinal surgery, BIS and spectral edge frequency (SEF95) were recorded at 3 different concentrations of halothane and isoflurane--namely 0.5, 0.75, and 1.0 MAC. The measurements were made both during wash-in and wash-out phases of the anesthetic agent. Eighteen patients received halothane and 16 received isoflurane. Heart rate, mean arterial pressure, oxygen saturation, and end tidal carbon dioxide pressure values were not different between the 2 groups at various MAC concentrations of the anesthetic agents. BIS and SEF95 values decreased significantly with increasing concentrations of both the anesthetic agents (P<0.001). At any given MAC concentration of the anesthetic, BIS and SEF(95) values were significantly lower under isoflurane compared with halothane anesthesia both during wash-in and wash-out phases (P<0.001). For a given anesthetic agent, BIS values were comparable at equi-MAC concentrations during wash-in and wash-out phases. In conclusion, BIS values are significantly lower under isoflurane compared with halothane anesthesia at similar MAC concentrations. For a given anesthetic agent and a given MAC concentration, the BIS values are similar during wash-in and wash-out phases of anesthesia.     

Sevoflurane titration using bispectral index decreases postoperative vomiting in phase II recovery after ambulatory surgery.

We tested the hypothesis that titration of sevoflurane using bispectral index (BIS) of the electroencephalogram decreases postoperative nausea and vomiting and improves recovery after outpatient gynecologic laparoscopy. After propofol induction, anesthesia was maintained in all patients with sevoflurane in 65% nitrous oxide and oxygen. In the BIS-Titrated group (n = 32), sevoflurane was titrated to maintain the BIS between 50 and 60 during surgery. In the Control group (n = 30), sevoflurane was adjusted to keep hemodynamic variables within 25% of control values. The severity of pain, postoperative nausea and vomiting, and recovery variables were recorded. In the Control group, 30% of the patients had BIS <40 during surgery (versus 0 in the BIS-Titrated group). Orientation and ability to drink were achieved earlier in the BIS group (P < 0.05). At 30 min after cessation of nitrous oxide, patients in the BIS group performed better in the psychomotor recovery test (P < 0.01). In Phase II recovery room, these patients had significantly less vomiting than the patients in the Control group (16% versus 40% of the patients, respectively, P < 0.05). No differences were found in times to achieve home readiness. IMPLICATIONS: In patients undergoing outpatient gynecologic laparoscopy, the monitoring of bispectral index decreases vomiting in Phase II recovery room, but it has no effect on the time to achieve home readiness.     

Ingestion of stimulant medications does not alter bispectral index or clinical depth of anesthesia at 1 MAC sevoflurane in children

Background/Aim: Children treated with stimulant medications for the behavioral management of attention deficit hyperactivity disorder (ADHD) may present for elective surgery. Stimulant medication is often continued until the morning of surgery to optimize perioperative behavior. It is unknown whether such stimulant drug ingestion can affect cerebral arousal and alter depth of anesthesia. A clinically relevant alteration in measured depth of anesthesia could form the basis for an evidence‐based recommendation that children taking stimulant medications require a change in the amount of anesthetic delivered or that they require routine monitoring of depth of anesthesia. Materials and Methods: Thirty‐four ASA 1 and 2 children aged between 5 and 16, presenting for elective day case surgery, were recruited. Seventeen had a diagnosis of ADHD and had taken stimulant medication on the day of surgery, and 17 were controls. A standard inhalational induction of anesthesia using air, oxygen, and sevoflurane by facemask was performed and maintained for 10 min at 1 MAC endtidal sevoflurane. During this time, no other stimulus was applied to the patient. Bispectral index (BIS) and other markers of depth of anesthesia were recorded after 10 min. Results: Children in both groups were of similar ages and weights. There were a higher percentage of boys in the stimulants group. Baseline physiological parameters were similar in both groups. After induction and equilibration for 10 min of anesthesia at 1 MAC endtidal sevoflurane, there was no significant difference in BIS or clinical markers of depth of anesthesia. Conclusions: Children taking stimulant medication for ADHD, and who ingest medication on the day of surgery, do not appear to have altered BIS or depth of anesthesia at 1 MAC of sevoflurane. These results do not support a recommendation for a change in anesthetic practice for children having ingested stimulants up to the day of surgery, either in terms of increasing the amount of anesthetic given or monitoring of depth.     

Median EEG frequency is more sensitive to increases in sympathetic activity than bispectral index.

Sympathetic heart rate variability is correlated with the increase in plasma catecholamines during rapid opioid detoxification. We evaluated whether the bispectral index, median frequency, or 95% spectral edge of the electroencephalogram are sensitive to the sympathetic response seen during reversal of opioid dependence. Eight patients undergoing rapid opioid detoxification gave informed consent. Two-channel frontal electroencephalogram was measured. Sympathetic heart rate variability was measured in 256 second segments by Fourier transform of continuous heart rate and the low frequency segment (0.02-0.13 Hz) analyzed for sympathetic function. Patients were anesthetized with propofol infusion. After a 30-60 min steady state, naloxone was infused intravenously at a rate of 25 mg/30 min, followed by an infusion of 1 mg/hr. During induction of anesthesia, sympathetic heart rate variability decreased from 1.80 to 0.3, bispectral index from 86 to 47, median frequency from 10.2 to 3.4, spectral edge from 23.5 to 16.7 (all P<.05). During naloxone infusion, the median percent increase in sympathetic heart rate variability was 487% (P<.05), median frequency increased 163% (P<.05), bispectral index (10%), and spectral edge (7%) did not significantly change. The increase in median frequency was delayed compared to sympathetic heart rate variability and median frequency remained elevated after sympathetic heart rate variability returned to anesthetized baseline in 5 of 8 cases. Our results show that median frequency and sympathetic heart rate variability increase during opioid detoxification, but the time course of each response is different. Median frequency is a more sensitive electroencephalogram indicator of opioid reversal than bispectral index or spectral edge.     

The impact of age on bispectral index values and EEG bispectrum during anaesthesia with desflurane and halothane in children

Background. The relationship between end-tidal sevoflurane concentration,bispectral index (BIS) and the EEG bispectrum in children appearsto be age dependent. The aim of this study was to quantify theBIS values at 1 MAC (minimum alveolar concentration) for desfluraneand halothane, and explore the relationship with age for theseanaesthetic agents in children. Methods. ECG, EEG and BIS were recorded continuously in 90 childrenaged 6–170 months requiring anaesthesia for elective surgery.Fifty children were anaesthetized with desflurane, and 40 childrenwith halothane. Recordings were performed through to a steadystate of 2 MAC, and thereafter at 1 and 0.5 MAC, respectively.The bispectrum of the EEG was estimated using MATLAB© software.A multiple correspondence analysis (MCA) was used. Results. At a steady state of 1 MAC, BIS values were significantlyhigher with halothane 62 (43–80) than desflurane 34 (18–64).BIS values were significantly correlated with age in both groups:DES (r²=0.57; P<0.01) and HALO (r²=0.48; P<0.01). Changesin position in the structured model of the MCA (dependent onthe pattern of the EEG bispectrum) were different for the twovolatile anaesthetic agents. Conclusions. In children, BIS values are linked to age irrespectiveof the volatile anaesthetic agent used. The difference in BISvalues for different agents at the same MAC can be explainedby the specific effect on the EEG bispectrum induced by eachanaesthetic agent, bringing into question the ability of theEEG bispectrum to accurately determine the depth of anaesthesia.     

Unusually low bispectral index values during emergence from anesthesia

We observed unusually low BIS values during emergence from anesthesia apparently caused by misanalysis (as "suppression") of low voltage electroencephalogram. IMPLICATIONS: When BIS values do not adequately correspond with clinical status, it is necessary to check raw electroencephalogram waveforms to more clearly characterize patient status.     

Clonidine decreases propofol requirements during anaesthesia: effect on bispectral index

Assessment of the effect of clonidine on depth of anaesthesiais difficult because clonidine combines analgesic, sedativeand direct haemodynamic effects. We thus evaluated the influenceof clonidine on the bispectral index (BIS) and its potentialdose-sparing effect on propofol. After induction of anaesthesiawith target-controlled infusion of propofol and obtaining anunchanged bispectral index (pre-BIS), clonidine 4 µg kg^–1or placebo was administered randomly to 50 patients in a double-blindmanner. Subsequently, if there was a decrease in BIS we reducedthe target concentration of propofol until pre-BIS was reached.The pre-BIS was maintained and a remifentanil infusion was addedduring surgery. The courses of the BIS, heart rate and bloodpressure were recorded and the total amounts of intra-operativepropofol and remifentanil were determined. Assessment of implicitmemory during anaesthesia was performed with an auditory implicitmemory test consisting of item sequences. Administration ofclonidine resulted in a decrease in the BIS from 45 (SD 4) to40 (6) (P<0.001), which allowed a reduction of propofol targetconcentration from 3.3 (0.6) to 2.7 (0.7) µg ml^–1(P<0.001) and measured propofol concentration from 2.9 (0.6)to 2.5 (0.7) µg ml^–1 (P=0.009) in order tomaintain the pre-BIS value. During subsequent surgery, propofolrequirements were reduced by 20% (P=0.002) in the clonidinegroup and a similar amount of remifentanil was used in eachgroup. The increase in anaesthetic depth given by clonidinecan therefore be measured with bispectral EEG analysis and allowsreduction of the propofol dose to achieve a specific depth ofanaesthesia. Br J Anaesth 2001; 86: 627–32     

Sevoflurane (0.4 MAC) does not influence cerebral compliance in healthy individuals

The use of sevoflurane is favored for its rapid onset and offset of anesthesia as well as good intraoperative titratability of the anesthetic. With regard to neuroanesthesia, the reported effects of sevoflurane on cerebral hemodynamics and cerebrospinal fluid dynamics are inconsistent. We used phase-contrast magnetic resonance imaging measurement of systolic cerebrospinal fluid peak velocity (CSFVPeak) to evaluate the effect of sevoflurane on cerebral compliance in healthy individuals. During administration of 0.4 MAC sevoflurane, systolic CSFVPeak in the aqueduct of Sylvius remained unchanged, thereby indicating unaffected cerebral compliance: (CSFVPeak baseline: -3.1 +/- 1.0 cm/s vs. sevoflurane: -3.0 +/- 1.2 cm/s). We conclude that low-dose administration of sevoflurane does not influence cerebral compliance in healthy individuals, but the influence of coexisting intracranial pathology or comedications on cerebral compliance requires further clinical investigation.     

Sevoflurane has less effect than halothane on pulmonary afferent activity in the rabbit

We have compared the effects of sevoflurane and halothane on the discharge frequencies of 19 slowly adapting and four rapidly adapting lung receptors in the rabbit by recording from single vagal fibres. Both agents reduced the discharge frequency of slowly adapting receptors during expiration (P < 0.0005), halothane having a greater effect than sevoflurane (P < 0.0005). Neither agent had any effect on discharge frequency at the end of inspiration when discharge frequency is at a maximum. Neither agent affected the discharge frequency of rapidly adapting receptors.      

Sevoflurane induces less cerebral vasodilation than isoflurane at the same A-line autoregressive index level

BACKGROUND: The use of sevoflurane in neuroanesthesia is still under debate. Comparison of dose-dependent vasodilatory properties between sevoflurane and isoflurane, the more traditional neuroanesthetic agent, requires comparable dosing of the agents. A-line autoregressive index (AAI) provides reproducible individual measurement of anesthetic depth. METHODS: Sevoflurane and isoflurane, in randomized order, were titrated to a stable AAI of 15-20 in each of 18 ASA I or II patients. The mean flow velocity (Vmca) and pulsatility index (PI) in the middle cerebral artery were measured with transcranial Doppler at an end-tidal CO2 of 4.5%. RESULTS: For sevoflurane Vmca was 18% lower [95% confidence interval (CI) 12-22%; P < 0.00001] and PI was 23% higher (95% CI 12-33%; P = 0.0013) than for isoflurane. Mean arterial blood pressure did not differ between the two agents. The minimum alveolar concentration (MAC) fraction necessary to reach the intended AAI level was 13% higher (95% CI 5-20%; P = 0.0079) with sevoflurane than with isoflurane. CONCLUSION: Sevoflurane induced less cerebral vasodilation than isoflurane at the same depth of anesthesia, measured by AAI, and hence seems more favorable for clinical neuroanesthesia. In our opinion the difference between sevoflurane and isoflurane in the MAC fraction required to attain the same AAI level demonstrates the limitations of MAC in defining the level of anesthesia.     

The correlation between bispectral index and airway reflexes with sevoflurane and halothane anaesthesia

Background: Unwanted airway reflexes such as laryngospasm are a frequent cause for concern in paediatric anaesthesia. They are more active during light anaesthesia. Bispectral index (BIS) is a recognized measure of anaesthetic effect. Ensuring adequate depth with the BIS may prevent these reflexes. This study investigates the relationship between BIS and a defined measure of airway reactivity. Methods: Sixty‐two children scheduled for direct laryngoscopy and bronchoscopy were enrolled in this prospective nonrandomized blinded study. They were induced and maintained with either sevoflurane or halothane. When depth of anaesthesia was judged deep enough on clinical grounds, the cords were sprayed with 2% lidocaine. Using an A2000 monitor, the BIS was recorded at the moment of spraying the cords. The anaesthetist was blinded to the BIS and noted whether or not spraying resulted in complete closure of the cords. Breath holding, desaturation and coughing were also recorded as secondary endpoints. Results: Using logistic regression there was a significant correlation between BIS and cord closure for halothane but not for sevoflurane (halothane Pseudo r² = 0.5, P = 0.003; sevoflurane Pseudo r² = 0.0004, P = 0.9). Although the study was not specifically designed to test for it, no difference was detected between agents in the incidence of cord closure (halothane 38%, sevoflurane 36%), or secondary endpoints (halothane 29%, sevoflurane 29%). Conclusions: The BIS may be useful to help prevent unwanted airway reflexes when using halothane but not with sevoflurane. The differing sites of anaesthetic action for sevoflurane and halothane may explain this result.     

Low bispectral index values following electroconvulsive therapy associated with memory impairment

Purpose  It has been reported some patients have opened eyes with low bispectral index (BIS) values immediately following electroconvulsive therapy (ECT). We investigated the time course of the recovery from amnesia and BIS values. Methods  Five patients with depression requiring repeated ECT procedures were enrolled. The patients were asked to recall an object presented prior to anesthesia at four specific points (prior to induction, upon regaining consciousness following ECT, when they returned to their ward, and when their BIS values had returned to pre-anesthetic levels). BIS data were recorded continuously until BIS values returned to the pre-anesthetic levels at their ward. The area under a receiver-operating characteristic (ROC) curve was used to detect associations between the BIS values and disturbance of memory function. Results  A total of 41 ECT stimuli were administered. After returning to their ward, patients generally fell asleep, with BIS values of between 50 and 70, and they woke up 1–2 h later. All the patients could recall the presented object prior to anesthesia and when the BIS values had returned to pre-anesthetic levels. The area under the ROC curve for the detection of memory disturbance was 0.902. Conclusion  The present study demonstrated a high frequency of patients falling asleep and the frequent occurrence of prolonged periods of low BIS values following ECT. The results of memory testing showed that ECT procedures resulted in amnesia. The ROC curve findings suggest a strong association of memory disturbance with BIS values. In conclusion, patients generally fell asleep, with low BIS values, for 1–2 h after ECT, and a prolonged period of impairment of memory formation was associated with low BIS values.