The effect of remifentanil on the middle latency auditory evoked response and haemodynamic measurements with and without the stimulus of orotracheal intubation.

BACKGROUND AND OBJECTIVE: Changes in the middle latency auditory evoked response following the administration of opioids have been shown. However, it remains unclear as to whether these changes are due to a direct depressant effect of opioids on the middle latency auditory evoked response itself, or an indirect effect on account of their action in attenuating central nervous system arousal associated with noxious stimuli. By comparing changes in the middle latency auditory evoked response in intubated and non-intubated patients, receiving saline or remifentanil in different doses, this study attempts to answer this question. METHODS: Fifty-four patients were anaesthetized with isoflurane and nitrous oxide (0.9 MAC) and randomized to 1-6 groups. Groups 1-3 received a bolus injection of either saline 0.9%, low-dose remifentanil (1 microg kg(-1)) or high-dose remifentanil (3 microg kg(-1)) prior to intubation of the trachea. Groups 4-6 were not intubated following the bolus injection. RESULTS: Pa and Nb amplitudes of the middle latency auditory evoked response increased by 82% and 79% with intubation in the saline group (P < 0.005) and these changes were not seen in the patients given remifentanil. There was a significant linear trend for the reduction in Pa and Nb amplitude with increasing remifentanil dose (P < 0.05). In the absence of endotracheal intubation remifentanil had no effect on either the amplitudes or latencies of the waves Pa and Nb and there was no effect of dose. For the haemodynamic measurements remifentanil attenuated the pressor response to intubation (P < 0.001) and had a significant dose-related effect (P < 0.001) in the absence of intubation. CONCLUSIONS: We demonstrated an effect of remifentanil on both the middle latency auditory evoked response and haemodynamic changes to endotracheal intubation. For the non-intubated patients there was only an effect of remifentanil on the haemodynamic measurements. This suggests that remifentanil has an effect on the middle latency auditory evoked response in attenuating the arousal associated with intubation of the trachea but has no effect in the absence of a stimulus.

Auditory evoked response during propofol anaesthesia after pre-induction with midazolam.

BACKGROUND: In clinical use, midazolam reduces the dose requirement for propofol. We studied the effect of midazolam given before anaesthesia on the amount of propofol needed and the time taken, to achieve loss of consciousness (LOC) in 20 patients. METHODS: We compared the auditory evoked responses (AER) in these patients with those in a group of 20 patients who were not given midazolam. RESULTS: LOC, as defined by a loss of response to verbal command and eyelash reflex, occurred after 113 (95% CI, 99-131) s in the control group and 75 (56-101) s in the midazolam group (P < 0.05). In the control group 2.3 (2.0-2.6) mg kg-1 propofol caused LOC compared with 1.3 (1.1-1.5) mg kg-1 in the group pretreated with midazolam (P < 0.001). Pa amplitude decreased by 60% in the control group and by 54% in the midazolam group while Nb latency increased by 24% in the control group and by 32% in the midazolam group following LOC. These differences were not significant. CONCLUSIONS: We confirmed that coinduction of anaesthesia with midazolam and propofol reduces the requirement of propofol. We also demonstrated that the AER reflects anaesthetic depth rather than plasma concentrations of anaesthetic drugs.

Effects of different concentrations of sevoflurane and desflurane on subcortical somatosensory evoked responses in anaesthetized, non-stimulated patients.

Twenty-four patients were recruited and given either sevoflurane or desflurane as their sole anaesthetic. Each patient was given sequentially increasing or decreasing doses at 0.5 MAC intervals, and the median nerve somatosensory evoked response recorded after an equilibration at each concentration. The N20-P25 and P25-N35 amplitudes decreased with increasing agent concentration. However, for both agents the P15-N20 amplitude response was quadratic in shape. The peak inflection points were at 3.2% for sevoflurane and 4.9% for desflurane. There were no differences between the ascending and descending groups. This increase in activity in the midbrain at 'surgical' end-tidal anaesthetic concentrations suggests more complex neuroelectrical responses to anaesthesia than simple global suppression.

Effect of tramadol on electroencephalographic and auditory-evoked response variables during light anaesthesia.

Tramadol is a centrally acting opioid-like analgesic commonly used for analgesia during surgery. It has been stated that the use of tramadol increases the risk of awareness during anaesthesia. We studied 29 patients under steady state anaesthesia, ventilated via a laryngeal mask airway with 0.6 MAC isoflurane in 50% nitrous oxide, and with no surgical stimulus. The electroencephalogram (EEG) and auditory-evoked response (AER) were recorded throughout the study period, as were pulse and arterial pressure. Patients were given randomly a bolus of either saline (S), tramadol 100 mg (T1), or tramadol 200 mg (T2). Significant increases in systolic arterial pressure and decreases in heart rate were seen in the tramadol groups compared to the saline group. Significant, dose-related activation in all EEG variables (median power frequency, spectral edge, Delta Power and Alpha/Delta ratio) but no significant change in Pa or Nb amplitudes or latencies were noted. The EEG changes were not at levels thought to be associated with awareness. This study indicates that tramadol, whilst causing EEG activation, has no effect on depth of anaesthesia as measured by the AER.

Effect of bolus doses of alfentanil on the arousal response to intubation, as assessed by the auditory evoked response.

We have studied the effect of bolus doses of alfentanil on the arousal response to intubation, using the auditory evoked response (AER) of the electroencephalogram (EEG) in 45 anaesthetized patients. After induction of anaesthesia with propofol and 20 min of positive pressure ventilation via a laryngeal mask airway with 0.6 MAC of isoflurane and 50% nitrous-oxide in oxygen, patients received saline (control), or alfentanil 15 or 50 micrograms kg-1 before intubation. The early cortical AER before and after intubation in each group was measured and compared. After intubation, Pa amplitude increased in the saline group by 60% (95% CI +10 to +130), decreased in the low-dose alfentanil group by 11% (-38 to +29) and decreased further in the high-dose alfentanil group by 26% (-49 to +7). There were significant (P < 0.005) linear trends in the three group means for Pa amplitude. Similarly, Nb latency increased in the saline group by 30% (-2 to +73), decreased in the low-dose alfentanil group by 10% (-32 to +19) and decreased further in the high-dose alfentanil group by 19% (-39 to +7). There were significant (P = 0.02) linear trends in the three group means for Nb amplitude. Systolic and diastolic arterial pressures increased after intubation in the control group, and to a lesser extent in the low-dose alfentanil group, but decreased after high-dose alfentanil. Heart rate increased after intubation in the control group but decreased in both alfentanil groups, decreasing to a greater degree in the high-dose group. There were significant (P < 0.001) linear trends for all three haemodynamic variables in the three groups. We conclude that the increase in Pa amplitude after intubation was blocked by bolus administration of alfentanil and that this effect was dose dependent.

Effect of a bolus dose of midazolam on the auditory evoked response in humans.

We have studied the effect of a bolus dose of midazolam on the auditory evoked response (AER) of the electroencephalogram (EEG) in nine patients. We measured the AER in the awake patient, at the point of loss of the eyelash reflex and when airway support was required. The eyelash reflex was lost at mean 1.78 (SD 0.5) min after administration of the midazolam bolus dose. Time to airway support in the seven patients who required it was 2.74 (1.26) min. Mean Nb latency in awake patients was 44.3 ms (95% CI 41.9-46.9) which was significantly shorter than Nb latency at the clinical end-points (P < 0.001). When the eyelash reflex was lost, Nb latency was 55.7 ms (95% CI 51.4-60.3) and when airway support was needed, it was 50.9 ms (95% CI 48.6-53.2). We conclude that loss of consciousness after midazolam was associated with an increase in mean Nb latency.

Auditory evoked response, median frequency and 95% spectral edge during anaesthesia with desflurane and nitrous oxide.

We have studied in 12 patients the effect of desflurane in nitrous oxide on the electroencephalogram (EEG) and the early cortical auditory evoked response (AER). After induction with desflurane, patients' lungs were ventilated to maintain three different end-expiratory concentrations of desflurane (1.5, 3 and 6%) during four consecutive 10-min periods before surgery. As the end-expiratory concentration of desflurane was increased, Pa and Nb (AER) amplitudes decreased and their latencies increased, and spontaneous EEG showed an increase in amplitude and a slowing of frequency. A linear relationship was demonstrated between log10 concentration of desflurane and all variables (P = 0.001). Pa amplitude showed the greatest linearity followed by the derived variable F95 of the EEG. From regression slopes, mean percentage changes of each variable were calculated for a 1 MAC change in desflurane concentration, Pa amplitude showed the largest change (mean 49% (95% confidence interval 40-56%) decrease for a 1 MAC increase). This was greater than that of F95 for a similar confidence interval, indicating better resolution. This study confirms that the early cortical AER is affected by desflurane in a similar manner to that of other anaesthetic agents and as such remains the most promising EEG derived measure of depth of anaesthesia.

Anesthesia for patients with carcinoid syndrome.

Carcinoid syndrome, although rare, can create serious problems to the anesthetist, both by the nature and variability of clinical manifestations and by the complications that can occur peroperatively. Recent research has led to a better understanding of the pathophysiology of the disease process. However, modern medicine is far from unraveling the precise nature and physiological effects of all the peptide mediators produced by these tumors. The severity of symptoms does not predict the severity of perioperative complications, so that patients with minor preoperative symptoms may have significant intraoperative complications. While urinary 5-HIAA levels provide a good indicator of disease progression, they cannot predict the degree or type of physiological response to intraoperative tumor manipulation. Indeed, urinary 5-HIAA may be normal both in the presence of a clinical diagnosis of carcinoid syndrome and in the face of a peroperative carcinoid crisis. The keys to successful anesthetic management of patients with carcinoid syndrome are good communication between endocrinologist, anesthetist, and surgeon and preoperative optimization of the patient. This includes appropriate investigation and treatment of the effects of carcinoid peptides and the prevention of their release from tumors. If possible, advice should be sought from centers with experience at managing this group of patients. Octreotide has largely replaced the use of other drugs both for symptomatic control and acute treatment of the symptoms associated with carcinoid syndrome. However, other drugs, such as aprotinin, still have a significant place in the symptomatic control and treatment of peroperative complications, as serotonin is only one of a large variety of peptides responsible for the clinical effects of this disease. Anesthetic technique should be aimed at minimizing carcinoid mediator release, in response to stress it induction of anesthesia and tracheal intubation and during tumor manipulation. It is equally important to prepare for carcinoid crisis by, for example, ordering drugs, which are otherwise uncommonly used in the theater setting, ahead of time. Cardiovascular instability, particularly hypotension, is common, so that full monitoring and vigilance is vital to predict its onset. The current surgical view of management is that, while curative resection of carcinoid tumors less than 2 cm in diameter with no evidence of invasion or metastatic spread is appropriate, patients with disseminated disease should be medically managed unless symptom control is poor. The exceptions to this are those patients with early and correctable carcinoid cardiac disease and those who require palliative procedures such as defunctioning obstructed bowel. Survival rates in patients following excision of gastric and appendical carcinoid tumors approach those of the general population as a whole and the chance of metastasis is extremely low. Only two series have been published in the anesthetic literature on anesthesia for patients with carcinoid syndrome, although there are many single-case reports. Despite the rarity of this syndrome, further formal studies into the anesthetic management of this condition should be encouraged.

Effect of suxamethonium on the auditory evoked response in humans.

We have studied the arousal effect of suxamethonium on the auditory evoked response (AER) of the electroencephalogram (EEG) in 40 ASA I and II patients during isoflurane anaesthesia. After induction of anaesthesia, the patient's lungs were ventilated for 20 min with 0.6 MAC end-expiratory isoflurane (0.59-0.77% depending on the age of the patient), and 50% nitrous oxide in oxygen. The patients were then allocated randomly to one of two groups: 21 received suxamethonium 1 mg kg-1, while 19 were given saline. The AER before and after administration of suxamethonium or saline was compared to determine the changes in Pa and Nb amplitudes and latencies. Pa amplitude after suxamethonium increased by 53% (95% confidence interval (CI) 15, 104%) compared with a reduction in Pa amplitude in the saline group of 19% (95% CI, -41, 12%) (P = 0.004) suggesting an arousal effect. Similarly, Nb amplitude increased in the suxamethonium group by 47% (95% CI, 3, 110%) and decreased in the saline group by 11% (95% CI, -33, 19%) (P = 0.03). We conclude that suxamethonium caused arousal according to the AER and postulate that this may have been caused by increased muscle afferent activity after stimulation of muscle spindles, although further studies are required to confirm this.

MAC reduction of isoflurane by sufentanil.

We have shown previously that a plasma fentanyl concentration of 1.67 ng ml-1 reduced the MAC of isoflurane by 50%. By comparing equal degrees of MAC reduction by sufentanil, we may determine the potency ratio of these opioids. Seventy-six patients were allocated randomly to receive predetermined infusions of sufentanil, and end-tidal concentrations of isoflurane in oxygen. Blood samples were obtained 10 min after the start of the infusion, and just before and after skin incision. Any purposeful movement by the patient was recorded. The MAC reduction of isoflurane produced by sufentanil was obtained using a logistic regression model. A sufentanil plasma concentration of 0.145 ng ml-1 (95% confidence limits 0.04, 0.26 ng ml-1) resulted in a 50% reduction in the MAC of isoflurane. At a plasma concentration greater than 0.5 ng ml-1, sufentanil exhibited a ceiling effect.