Ira J. Rampil

Anesthetic Potency (MAC) Is Independent of Forebrain Structures in the Rat

BackgroundThe ability of general anesthetics to suppress somatomotor responses to surgical incision and other noxious stimuli is of particular clinical relevance. When the blockade is due to inhaled agents, this effect can be quantified as the minimum alveolar concentration (MAC), i.e., that concentration that blocks movement evoked by a noxious stimulus (ED50). MethodsTo identify the neural structures that subtend this somatomotor response, we anesthetized 14 rats with isoflurane in oxygen and performed bilateral parietal-temporal craniotomles. In each rat, MAC was repeatedly tested using tail-clamping and Dixons up-down concentration technique. After determination of baseline MAC, seven rats underwent aspiration decerebration, after which MAC was repeatedly measured. ResultsIn the control group (N = 7), MAC (mean ± SD) remained constant at 1.30 ± 0.25% for more than 6 h. In the seven rats that underwent aspiration decerebration, baseline MAC was 1.26 ± 0.14%. These seven rats with histologically validated precollicular decerebration demonstrated no change in MAC relative to control rats, as much as 11 h after decerebration (P = 0.14). ConclusionsThese findings suggest that the anesthetic-induced unresponsiveness to noxious stimuli measured by MAC testing does not depend on cortical or forebrain structures in the rat.

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

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.

Anesthetic potency is not altered after hypothermic spinal cord transection in rats.

BackgroundIn essence, the clinical goal of general anesthesia is to produce a state of unresponsiveness and amnesia. These endpoints are commonly achieved with drugs like isoflurane, but the sites and mechanisms by which these specific endpoints are achieved remain unknown. Blocking the somatic motor response to painful stimuli is widely used as an indicator of anesthetic adequacy, and the concentration of anesthetic agent (minimum alveolar concentration [MAC]) required to achieve this unresponsiveness is the benchmark of anesthetic potency. Recent work has demonstrated that precollicular decerebration does not alter MAC in rats, suggesting that the forebrain is not a major site of action of isoflurane in blocking motor responses. The brain stem contains systems that modulate pain processing in the spinal cord. The current study was undertaken to assess the relative roles of the brain stem and spinal cord as sites of anesthetic action in blocking somatic responsiveness. MethodsIn seven rats, anesthesia was induced and maintained with isoflurane in oxygen. MAC was determined by observing the response to tail clamp and fore- and hind limb toe pinch at three times: after intubation, after cervical laminectomy, and after staged hypothermic spinal cord transection. ResultsMAC determined by tail clamp did not change during the protocol (1.28 ± 0.08% [mean ± standard deviation] baseline vs. 1.25 ± 0.18% postlaminectomy vs. 1.03 ± 0.40% posttransection). In one animal, the MAC value decreased from a prelesion value of 1.2% to 0.25%, accounting for most of the variance in the postlesion mean; the MAC value as determined by withdrawal to rear paw pinch was unchanged from its prelesion value in this animal. The MAC values as determined by toe pinch in all animals remained unchanged after spinal transection of the lesion both rostrally and caudally. ConclusionsSomatic motor responsiveness and its sensitivity to isoflurane appeared to be unaltered despite acute loss of descending cortical and bulbar controls. This observation suggests that the site of anesthetic inhibition of motor response may be in the spinal cord.

Performance of the ARX-derived auditory evoked potential index as an indicator of anesthetic depth: a comparison with bispectral index and hemodynamic measures during propofol administration.

Background Autoregressive modeling with exogenous input of middle-latency auditory evoked potential (A-Line autoregressive index [AAI]) has been proposed for monitoring anesthetic depth. The aim of the current study was to compare the accuracy of this new index with the Bispectral Index (BIS), predicted effect-site concentration of propofol, and hemodynamic measures. Methods Twenty female patients scheduled for ambulatory gynecologic surgery received effect compartment controlled infusion of propofol. Target effect-site concentration was started at 1.5 &mgr;g/ml and increased every 4 min by 0.5 &mgr;g/ml. At every step, sedation level was compared with monitoring values using different clinical scoring systems and reaction to noxious stimulus. Results Bispectral Index, AAI, and predicted propofol effect-site concentration were accurate indicators for the level of sedation and loss of consciousness. Hemodynamic variables were poor indicators of the hypnotic-anesthetic status of the patient. BIS correlated best with propofol effect-site concentration, followed by AAI. Hemodynamic measurements did not correlate well. No indicators predicted reaction to noxious stimulus. Poststimulus, BIS and AAI showed an increase as a result of arousal. This reaction occurred more rapidly with the AAI than with BIS. Conclusion Bispectral Index, AAI, and predicted propofol effect-site concentration revealed information on the level of sedation and loss of consciousness but did not predict response to noxious stimulus.

Bispectral EEG Index during Nitrous Oxide Administration

Background Nitrous oxide (N2 O) is a commonly used sedative for painful diagnostic procedures and dental work. The authors sought to characterize the effects of N2 O on quantitative electroencephalographic (EEG) variables including the bispectral index (BIS), a quantitative parameter developed to correlate with the level of sedation induced by a variety of agents. Methods Healthy young adult volunteers (n = 13) were given a randomized sequence of N2 O/O2 combinations via face mask. Five concentrations of N2 O (10, 20, 30, 40, and 50% atm) were administered for 15 min (20 min for the first step). EEG was recorded from bilateral frontal poles continuously. At the end of each exposure, level of sedation was assessed using primarily the Observer Assessment of Alertness/Sedation (OAA/S) scale. Results One subject withdrew from the study because of emesis at 50% N (2) O. N2 O (50%) increased theta, beta, 40 - 50 Hz, and 70 - 110 Hz band powers. BIS and spectral edge frequency during 50% N2 O/O2 did not differ significantly from baseline values. Abrupt decreases from higher to lower concentrations frequently evoked a profound, transient slowing of activity. No significant change in OAA/S was detected during the study. Conclusions Although the spectral content of the EEG changed during N (2) O administration, reflecting some pharmacologic effect, the subjects remained cooperative and responsive throughout, and therefore N2 O can only be considered a weak sedative at the tested concentrations. Despite changes in the lower and higher frequency ranges of EEG activity, the BIS did not change, which is consistent with its design objective as a specific measure of hypnosis.

Clinical characteristics of desflurane in surgical patients : minimum alveolar concentration

Desflurane (formerly I-653) is a new inhalaticnal anesthetic with a promising pharmacokinetic profile that includes low solubility in blood and tissue, including fat. Since its lipid solubility is less than that of other volatile agents, it may have lower potency. Low solubility would be expected to increase the rate at which alveolar concentration approaches inspired concentration during induction as well as to increase the rate of elimination of desflurane from blood at emergence. We determined the minimum alveolar concentration (MAC) of desflurane in 44 unpremedicated ASA physical status 1 or 2 patients undergoing elective surgery. We prospectively studied four patient groups distinguished by age and anesthetic regimen: 18-30 versus 31-65 yr and desflurane in 60% N2O/40% O2 versus desflurane in O2. Anesthesia was induced with desflurane or desflurane in 60% N2O/40% O2. MAC was determined by a modification of Dixons up-and-down method with increments of 0.5% desflurane. The MAC of desflurane in O2 was 7.25 +/- 0.0 (mean +/- SD) in the 18-30-yr age group, and 6.0 +/- 0.29 in the 31-65-yr group; the addition of 60% N2O reduced the MAC to 4.0 +/- 0.29 and 2.83 +/- 0.58, respectively. The median time from discontinuation of desflurane to an appropriate response to commands was 5.25 min. Desflurane appears to be a mild airway irritant but was well tolerated by all patients.

No correlation between quantitative electroencephalographic measurements and movement response to noxious stimuli during isoflurane anesthesia in rats.

A meaningful use of the electroencephalogram (EEG) for monitoring depth of anesthesia has proven elusive. Although changes in the EEG with changing anesthetic dose or concentration have been noted for 60 yr, it has been difficult to demonstrate reliable, quantitative correlation between the EEG and other physiologic measures of anesthetic depth. We attempted to correlate several quantitative EEG measurements in rats, including average amplitude, spectral edge frequency, and burst suppression ratio, with the movement response to supramaximal noxious stimulation. We anesthetized 21 Sprague-Dawley rats with isoflurane 1.5% and allowed them to breathe spontaneously. After equilibration, EEG was recorded for off-line analysis; then a noxious stimulation was delivered with a tail clamp and the somatic response noted. Isoflurane concentration was adjusted up and down, and the EEG and movement response to tail clamp were assessed at each level until the minimum alveolar concentration was determined in each rat. We found no EEG dose response to increasing inspired concentrations of isoflurane, except for an increasing degree of burst suppression. We found no difference in any parameter between rats that responded and those that did not respond to stimuli at a given concentration of isoflurane. Finally, we found that the presence of burst suppression did not predict lack of response.

Volatile Anesthetics Depress Spinal Motor Neurons

Background Depression of spinal alpha-motor neurons apparently plays a role in the surgical immobility induced by isoflurane. Using the noninvasive technique of F-wave analysis, the authors tested the hypothesis that depressed motor neuron excitability is an effect common to other clinically relevant inhaled anesthetics. Methods The authors measured F-wave amplitude in rats anesthetized with desflurane, enflurane, halothane, or sevoflurane. Each animal received one anesthetic at five equipotent anesthetic concentrations (0.6, 0.8, 1.2, and 1.6 minimum alveolar concentration [MAC] and 0.8 MAC with 65% N2 O). F waves were detected as late potentials in electromyographic responses evoked in the intrinsic muscles of the hind paw after monopolar stimulation of the ipsilateral posterior tibial nerve. Results All tested inhaled anesthetics depressed F-wave amplitude but not M-wave (orthodromic, early muscle activation) amplitude, and increased M-F latency in a dose-dependent manner. At 1.0 MAC, the estimated F/M ratio was 70+/-13% SD of that at baseline (0.6 MAC). Nitrous oxide added to 0.8 MAC of the potent vapors depressed F/M ratio by 63+/-17%. Conclusions All anesthetics tested appeared to depress the excitability of spinal motor neurons. This effect may contribute to surgical immobility, and its magnitude is comparable at equipotent concentrations of agents. The authors hypothesize that this effect is due to hyperpolarization, although, currently, there is insufficient information to discriminate between pre- and postsynaptic mechanisms.

The Electroencephalogram Does Not Predict Depth of Isoflurane Anesthesia

BackgroundThe power spectrum of the electroencephalogram (EEG) may be analyzed to provide quantitative measures of EEG activity (e.g., spectral edge, which defines the highest EEG frequency at which significant activity is found). The current study tested the hypothesis that spectral edge and similar measures distinguish different functional depths of anesthesia in humans. MethodsThree groups were studied. Group 1 consisted of 34 surgical patients (ASA physical status 1 or 2) who received 0.6, 1.0 and 1.4 MAC isoflurane anesthesia. A subgroup (group 2) of group 1 was tested during 1.0 MAC isoflurane anesthesia at surgical incision. Group 3 consisted of 16 volunteers who listened to an audiotape while receiving 0.15, 0.3, and 0.45 MAC isoflurane or 0.3, 0.45, and 0.6 MAC nitrous oxide in oxygen. The audiotape contained information designed to test implicit and explicit memory formation. We tested the ability of six EEG parameters (spectral-edge, 95th percentile power frequency, median power, and zero crossing frequencies and total power in the α- [8–13 Hz] and δ- [<4 Hz] power ranges) to predict movement after surgical incision, purposeful response to command, or memory of information presented during anesthetic administration. ResultsIsoflurane decreased EEG activity in group 1 in a dose-related fashion. The 55% of group 2 who made purposeful movements in response to incision did not differ in their EEG from nonresponders (e.g., spectral edge 19.8 ± 3.1 vs. 19.3 ± 2.6 Hz, mean ± SD). In group 3, memory of the information presented did not correlate with values of any EEG parameter. Response to verbal command was associated with lower anesthetic concentrations and with smaller α- and δ-band power (298 ± 66 vs. 401 ± 80 watts; and 75 ± 20 vs. 121 ± 49 watts, mean ± SD), but there was no difference in values for other parameters. ConclusionsWe conclude that our EEG measures do not predict depth of anesthesia as defined by the response to surgical incision, the response to verbal command or the development of memory.

Prognostic value of computerized EEG analysis during carotid endarterectomy

A single-channel EEG, analyzed in real time to produce a density spectral array (DSA) display was recorded during 111 carotid endarterectomies. A simple protocol that emphasized loss of high frequency activity was used to identify serious ischemic EEG events. In 70 patients (78 operations) with no preoperative neurologic deficits, new postoperative neurologic deficits appeared only in the seven patients who had ischemic EEG events that lasted 10 min or longer. The EEG was not predictive in the 31 patients (33 operations) who had preoperative neurologic deficits: one patient with no intraoperative change in EEG developed a new postoperative deficit, and one patient with EEG changes lasting 13 min had no demonstrable new deficit postoperatively. This EEG monitoring technique was simple and convenient to use, and appears to be predictive of gross neurologic outcome following carotid endarterectomy in patients without preoperative neurologic deficits.