Influence of 0.1 minimum alveolar concentration of sevoflurane, desflurane and isoflurane on dynamic ventilatory response to hypercapnia in humans

The purpose of this study was to quantify in humans the effects of subanesthetic isoflurane on the ventilatory control system, in particular on the peripheral chemoreflex loop. Therefore we studied the dynamic ventilatory response to carbon dioxide, the effect of isoflurane wash-in upon sustained hypoxic steady-state ventilation, and the ventilatory response at the onset of 20 min of isocapnic hypoxia. Study 1: Square-wave changes in end-tidal carbon dioxide tension (7.5-11.5 mmHg) were performed in eight healthy volunteers at 0 and 0.1 minimum alveolar concentration (MAC) isoflurane. Each hypercapnic response was separated into a fast, peripheral component and a slow, central component, characterized by a time constant, carbon dioxide sensitivity, time delay, and off-set (apneic threshold). Study 2: The ventilatory changes due to the wash-in of 0.1 MAC isoflurane, 15 min after the induction of isocapnic hypoxia, were studied in 11 healthy volunteers. Study 3: The ventilatory responses to a step decrease in end-tidal oxygen (end-tidal oxygen tension from 110 to 44 mmHg within 3-4 breaths; duration of hypoxia 20 min) were assessed in eight healthy volunteers at 0, 0.1, and 0.2 MAC isoflurane. Values are reported as means +/- SF. Study 1: The peripheral carbon dioxide sensitivities averaged 0.50 +/- 0.08 (control) and 0.28 +/- 0.05 l.min-1.mmHg-1 (isoflurane; P < 0.01). The central carbon dioxide sensitivities (control 1.20 +/- 0.12 vs. isoflurane 1.04 +/- 0.11 l.min-1.mmHg-1) and off-sets (control 36.0 +/- 0.1 mmHg vs. isoflurane 34.5 +/- 0.2 mmHg) did not differ between treatments. Study 2: Within 30 s of exposure to 0.1 MAC isoflurane, ventilation decreased significantly, from 17.7 +/- 1.6 (hypoxia, awake) to 15.0 +/- 1.5 l.min-1 (hypoxia, isoflurane). Study 3: At the initiation of hypoxia ventilation increased by 7.7 +/- 1.4 (control), 4.1 +/- 0.8 (0.1 MAC; P < 0.05 vs. control), and 2.8 +/- 0.6 (0.2 MAC; P < 0.05 vs. control) l.min-1. The subsequent ventilatory decrease averaged 4.9 +/- 0.8 (control), 3.4 +/- 0.5 (0.1 MAC; difference not statistically significant), and 2.0 +/- 0.4 (0.2 MAC; P < 0.05 vs. control) l.min-1. There was a good correlation between the acute hypoxic response and the hypoxic ventilatory decrease (r = 0.9; P < 0.001). The results of all three studies indicate a selective and profound effect of subanesthetic isoflurane on the peripheral chemoreflex loop at the site of the peripheral chemoreceptors. We relate the reduction of the ventilatory decrease of sustained hypoxia to the decrease of the initial ventilatory response to hypoxia.

Effect of arousal on hypercapnic ventilatory response needs to be examined

To determine the minimum alveolar concentration (MAC) and hemodynamic responses to halothane, isoflurane, and sevoflurane in newborn swine, 36 fasting swine 4-10 days of age were anesthetized with one of the three volatile anesthetics in 100% oxygen. MAC was determined for each swine. Carotid artery and internal jugular catheters were inserted and each swine was allowed to recover for 48 h. After recovery, heart rate (HR), systemic systolic arterial pressure (SAP), and cardiac index (CI) were measured awake and then at 0.5, 1.0, and 1.5 MAC of the designated anesthetic in random sequence. The (mean +/- SD) MAC for halothane was 0.90 +/- 0.12%; the MAC for isoflurane was 1.48 +/- 0.21%; and the MAC for sevoflurane was 2.12 +/- 0.39%. Awake (mean +/- SD) measurements of HR, SAP, and CI did not differ significantly among the three groups. Compared to the awake HR, the mean HR decreased 35% at 1.5 MAC halothane (P less than 0.001), 19% at 1.5 MAC isoflurane (P less than 0.005), and 31% at 1.5 MAC sevoflurane (P less than 0.005). Compared to awake SAP, mean SAP measurements decreased 46% at 1.5 MAC halothane (P less than 0.001), 43% at 1.5 MAC isoflurane (P less than 0.001), and 36% at 1.5 MAC sevoflurane (P less than 0.005). Mean SAP at 1.0 and 1.5 MAC halothane and isoflurane were significantly less than those measured at equipotent concentrations of sevoflurane (P less than 0.005). Compared to awake CI, mean CI measurements decreased 53% at 1.5 MAC halothane (P less than 0.001) and 43% at 1.5 MAC isoflurane (P less than 0.005).(ABSTRACT TRUNCATED AT 250 WORDS)

To determine the effects of isoflurane and halothane on cerebrovascular reactivity to CO2, 30 children aged one to six years were anaesthetized with isoflurane or halothane in an air and oxygen mixture with an FIO2 of 0.3. The end-tidal concentrations (0.5 minimum alveolar concentration (MAC) or 1.0 MAC) of isoflurane or halothane were age-adjusted. After achieving a steady-state at both 0.5 MAC and 1.0 MAC isoflurane and halothane, the end-tidal carbon dioxide tension (PETCO2) was randomly adjusted to 20, 40, or 60 mmHg. Cerebral blood flow velocity (CBFV) and the cerebrovascular resistance index (RI+) in the middle cerebral artery (MCA) were measured by a transcranial Doppler monitor. Three measurements of CBFV and RI+ were obtained at each PETCO2 and isoflurane or halothane concentration. Any rise in the PETCO2 caused an increase in CBFV during both 0.5 MAC (r2 = 0.99 and 0.99) and 1.0 MAC (r2 = 0.96 and 0.95) isoflurane and halothane anaesthesia, respectively (P less than 0.05). The CBFV for isoflurane increased as PETCO2 increased from 20 to 60 mmHg for both 0.5 MAC and 1.0 MAC (P less than 0.05). The CBFV for halothane increased as PETCO2 increased from 20 to 40 mmHg for both 0.5 MAC and 1.0 MAC halothane (P less than 0.05), but did not change as PETCO2 increased from 40 to 60 mmHg for both 0.5 MAC and 1.0 MAC halothane. The RI+ showed an inverse relationship with CBFV at each PETCO2 for 0.5 MAC (r2 = 0.98 and 0.99) and 1.0 MAC (r2 = 0.76 and 0.53) isoflurane and halothane, respectively (P less than 0.05). The CBFV did not differ significantly between 0.5 and 1.0 MAC isoflurane and halothane at corresponding PETCO2 values. The cerebrovascular response to CO2 at 20 mmHg between 0.5 MAC and 1.0 MAC halothane was not significantly different. These data strongly suggest that isoflurane and halothane in doses up to 1.0 MAC do not affect the cerebrovascular reactivity of the MCA to CO2 in anaesthetized, healthy children.

Rarely, fire and patient injury result from the degradation of sevoflurane by desiccated Baralyme. The present investigation sought to determine whether high temperatures also arose with sevoflurane use in the presence of desiccated soda lime. We desiccated soda lime by directing a 10 L/min flow of oxygen through fresh absorbent. Using 1140 +/- 30 g (mean +/- sd) of this desiccated absorbent, we filled a single standard absorber canister placed in a standard anesthetic circuit to which we directed a 6 L/min flow of oxygen containing 1.5 minimum alveolar concentration (MAC) desflurane or sevoflurane, or 3.0 MAC desflurane, isoflurane, or sevoflurane (with and without concurrent delivery of 200 mL/min carbon dioxide). In an additional test, 2 canisters (rather than a single canister) containing desiccated absorbent were used and 3.0 MAC sevoflurane was applied. A 3-L reservoir bag served as a surrogate lung, and we ventilated this lung with a minute ventilation of 10 L/min. With desflurane at 1.5 MAC or 3.0 MAC or isoflurane at 3.0 MAC temperatures increased in 20 to 40 min to a peak of 30 degrees C to 45 degrees C and then declined. With 1.5 or 3.0 MAC sevoflurane, temperatures increased to approximately 90 degrees C, after which temperatures declined. Concurrent delivery of carbon dioxide and sevoflurane did not increase the peak temperatures reached. The use of 2 canisters increased the duration but not the peak of increased temperature reached with 3.0 MAC sevoflurane. No fires resulted from degradation of any anesthetic.

Morbid obesity affects the pharmacokinetics and pharmacodynamics of anesthetics, which may result in inappropriate dosing. We hypothesized that obesity significantly alters the minimum alveolar concentration (MAC) for isoflurane and sevoflurane. To test this hypothesis, we used a rodent model of human metabolic syndrome developed through artificial selection for inherent low aerobic capacity runners (LCR) and high aerobic capacity runners (HCR). The LCR rats are obese, display phenotypes homologous to those characteristic of human metabolic syndrome, and exhibit low running endurance. In contrast, HCR rats have high running endurance and are characterized by improved cardiovascular performance and overall health. Male and female LCR (n = 10) and HCR (n = 10) rats were endotracheally intubated and maintained on mechanical ventilation with either isoflurane or sevoflurane. A bracketing design was used to determine MAC; sensory stimulation was induced by tail clamping. An equilibration period of 30 minutes was provided before and between the consecutive tail clamps. Two-tailed parametric (unpaired t test) and nonparametric (Mann-Whitney test) statistics were used for the comparison of MAC between LCR and HCR rats. The data are reported as mean ± sd along with the 95% confidence interval. A P value of <0.05 was considered statistically significant. The MAC for isoflurane in LCR rats (1.52% ± 0.13%) was similar to previously reported isoflurane-MAC for normal rats (1.51% ± 0.12%). The HCR rats showed a significantly higher isoflurane-MAC (1.90% ± 0.19%) than did the LCR rats (1.52% ± 0.13%) (P = 0.0001). The MAC for sevoflurane was not significantly different between LCR and HCR rats and was similar to the previously published sevoflurane-MAC for normal rats (2.4% ± 0.30%). There was no influence of sex on the MAC of either isoflurane or sevoflurane. Obesity and associated comorbidities do not affect anesthetic requirements as measured by MAC in a rodent model of metabolic syndrome. By contrast, high aerobic capacity is associated with a higher MAC for isoflurane and may be a risk factor for subtherapeutic dosing.

The peripheral chemoreceptors are responsible for the ventilatory response to hypoxia (acute hypoxic response) and for 30% of the normoxic hypercapnic ventilatory response. To quantify the effects of subanesthetic concentrations of halothane on the respiratory control system, in particular on the peripheral chemoreceptors, we studied the response of humans to carbon dioxide and oxygen at two subanesthetic concentrations of halothane. Square-wave changes in end-tidal carbon dioxide tension (7.5-11.3 mmHg) and step decreases in end-tidal oxygen tension (arterial hemoglobin oxygen saturation 82 +/- 2%; duration of hypoxia 5 min) were performed in nine healthy male subjects during 0, 0.05 (HA-1), and 0.1 minimum alveolar concentration (HA-2) halothane. Each hypercapnic response was separated into a fast, peripheral component and a slow, central component, characterized by a time constant, carbon dioxide sensitivity, time delay, and off-set. Fifty-six carbon dioxide responses and 27 oxygen responses were obtained. The peripheral carbon dioxide sensitivities averaged to 0.76 +/- 0.14 l.min-1.mmHg-1 (control), 0.50 +/- 0.12 l.min-1.mmHg-1 (HA-1), and 0.30 +/- 0.08 l.min-1.mmHg-1 (HA-2; P < 0.01 vs. control). The central carbon dioxide sensitivity did not differ significantly among treatment groups (control, 1.47 +/- 0.22 l.min-1.mmHg-1; HA-1, 1.41 +/- 0.51 l.min-1.mmHg-1; and HA-2, 1.23 +/- 0.30 l.min-1.mmHg-1). The time constants of the central chemoreflex loop showed a large decrease during the administration of 0.1 minimum alveolar concentration halothane. The acute hypoxic response declined from 15.0 +/- 3.9 l.min-1 to 10.9 +/- 2.9 l.min-1 (HA-1) and 4.8 +/- 1.4 l.min-1 (HA-2; P < 0.01 vs. control and HA-1). All values are means +/- SEM. The results show depression of the ventilatory responses to hypoxia and hypercapnia during inhalation of subanesthetic concentrations of halothane. The depression is attributed to a selective effect of halothane on the peripheral chemoreflex loop. The oxygen and carbon dioxide responses mediated by the peripheral chemoreceptors are affected proportionally. It is argued that the decrease in central time constants is caused by an effect of halothane on central neuronal dynamics.

Received from the Department of General Anesthesiology, The Cleveland Clinic Foundation, Cleveland, Ohio.EVOKED potentials (EPs) are the electrophysiologic responses of the nervous system to sensory or motor stimulation. 1,2Stimulating the nervous system initiates the transmission of neural signals that may be recorded as EPs from various points along the stimulated pathway. Intraoperative monitoring (IOM) of EP has gained popularity because EPs reflect the functional integrity of neural pathways in anesthetized patients undergoing surgical procedures that place nervous system structures in jeopardy. EPs monitored intraoperatively include somatosensory evoked potentials (SSEPs), brainstem auditory evoked potentials (BAEPs; also referred to as auditory brainstem responses), visual evoked potentials (VEPs), and motor evoked potentials. Additional EP modalities include dermatomal sensory evoked potentials, electrocochleography, and electromyography.Intraoperative EP changes may result from surgical injury or ischemia of the specific neural pathway, or they may be due to nonspecific physiologic or pharmacologic influences. Physiologic factors that may influence EPs include temperature, blood pressure, hematocrit, acid–base balance, and oxygen and carbon dioxide tensions. Anesthetic drugs and sedatives are the most common pharmacologic causes of nonspecific EP changes.This review discusses the physiologic and pharmacologic factors (including newer anesthetic agents and adjuncts) that influence sensory evoked potentials (SEPs), focussing on SSEPs, BAEPs, and VEPs. For ease of reference and to allow better comparisons between anesthetic agents, the discussion of anesthetic effects is separated from physiologic effects. The review intends to help clinicians recognize the important confounding perturbations so that intraoperative changes in SEPs can be interpreted optimally. It also aims to guide anesthetic planning so that reliable intraoperative EP monitoring can be accomplished during effective and safe anesthesia.The single cortical sensory evoked response has a low amplitude (1–2 μV) compared with the much larger electroencephalogram waves (50–100 μV). Therefore, the EP wave has to be extracted from concurrent spontaneous electroencephalogram activity by repetitive stimulation and computer-signal averaging techniques. 3The EP waveform consists of a series of peaks and valleys presented as a graph of voltage over time and described in terms of amplitude, latency, and morphology. For IOM, amplitude is commonly measured as the waves’ peak-to-peak voltage difference. Latency is the time from stimulus to the peak of the response. Interpeak latency is the interval between the peaks of interest (fig. 1).Evoked potential waves can have either negative or positive polarity. A negative wave occurring at a latency of approximately 20 ms would be indicated as N-20. Generally, negative waves are shown as upward deflections, while positive waves are shown as downward deflections. Evoked potentials can be of cortical or subcortical origin. Responses recorded by electrodes located within 3–4 cm of the neural generator are termed near-field potentials (e.g. , cortical SSEP waves recorded from scalp electrodes), whereas those recorded from electrodes farther from the neural generator are called far-field potentials (e.g. , BAEP recorded over the vertex). 4,5SEPs are also classified as short latency (&lt; 30 ms), intermediate latency (30–75 ms), or long latency (&gt; 75 ms). 6For the purposes of this review, SEPs are considered recordable when reproducible waveforms are reported. An anesthetic regimen is described as compatible with IOM when it results in consistently recordable waveforms. Reliability of SEPs refers to their ability to detect potentially injurious conditions intraoperatively.The SSEP represents the reproducible electrical activity of cortical and subcortical structures time-locked to a peripheral nerve stimulus. For perioperative applications, electrical impulses are commonly delivered to the median nerve or posterior tibial nerves using needle or surface electrodes. The impulse propagates peripherally (resulting in muscle twitches) and centrally via the peripheral nerve and the dorsal root to the spinal cord. The nerve cell body of the first-order neuron lies in the dorsal root ganglion. Impulses then ascend primarily in the dorsal column fibers of the spinal cord, which synapse (fig. 2) in the lower medulla near the nucleus gracilis and cuneatus, respectively. Axons of the second-order neurons cross the midline at the cervicomedullary junction, from where they regroup to form the medial lemniscus and synapse in the ventroposterior–lateral nucleus of the contralateral thalamus. Third-order neurons from the ventroposterior–lateral leave the thalamus and travel through the posterior limb of the internal capsule as the thalamocortical radiation to synapse in the primary somatosensory cortex in the postcentral gyrus of the parietal lobe. The spinocerebellar pathways, located anteriorly in the spinal cord, contribute to the rostral conduction of SSEP signals. Therefore, SSEPs can assess the sensory system from the peripheral nerves through the spinal cord and brainstem to the cerebral cortex.Somatosensory evoked potential waveform activity can be recorded at the popliteal fossa after posterior tibial nerve stimulation and at Erb's point above the clavicle after median nerve stimulation. Spinal potentials recorded over the cervical and lumbar spinous processes confirm the delivery of the stimulus to the central neural axis, after it is delivered in the arm or leg, respectively. The subcortical component of the SSEP is recorded over the second cervical vertebra as a negative deflection (N-14) 14 ms after median nerve stimulation. The earliest cortical (midlatency) component of the SSEP wave is generated by the primary somatosensory cortex and occurs approximately 20 ms after median nerve and 40 ms after posterior tibial nerve stimulation. Cortical SSEPs are recorded from scalp overlying the contralateral primary sensory cortex (fig. 3). A spinal sensory EP may be stimulated or recorded from epidural electrodes placed percutaneously or in the surgical field. The central conduction time (CCT) is the time needed for the signal to travel from the cervicomedullary junction to the contralateral cerebral cortex (CCT = N-20 to N-14 latency difference after median nerve stimulation).The subcortical SSEP recorded over the second cervical vertebra can be very useful intraoperatively because it is not very susceptible to anesthetic effects. 7Assuming an electromyography artifact is eliminated and technical problems are solved, the cervical response has a shorter acquisition time that allows faster feedback to the surgical team, which enhances its usefulness in surgical procedures that may jeopardize the spinal cord. The midlatency cortical SSEP is moderately sensitive to anesthetic depression, but clinically useful recordings can be obtained in most patients with modifications in anesthetic technique. Longer latency SSEP waves, which represent further neural processing of sensory inputs into the association cortex, are exquisitely sensitive to anesthetic drugs, and therefore, are not useful to monitor the integrity of the sensory pathway. 8Diagnostic criteria to evaluate intraoperative waveform changes diagnostic of spinal cord dysfunction have been difficult to establish. Latency changes of 7–10% and amplitude decreases of 45–50% may occur without changes in postoperative neurologic function. 9–11The criteria for determining which event-related changes 10should be considered significant are still empiric. 12In patients undergoing surgical correction of neuromuscular scoliosis, sensitivity and specificity of IOM in the detection of new postoperative neurologic deficits was maximized with the use of a 50% amplitude reduction criterion. 13An alternate criterion for sounding the alarm intraoperatively has been loss of cortical baseline amplitude greater than 30–40%. 14–16Most, however, consider a decrease in amplitude of 50% or greater, an increase in latency of 10% or greater, or both to be significant changes reflecting loss of integrity of a neural pathway, provided these changes are not caused by anesthetics or temperature. 17–20At least one study suggests that the use of amplitude criteria is associated with better sensitivity for detecting neurologic injury than latency criteria. 21General anesthesia has an inhibitory effect on neurotransmission and, therefore, on the EP. The effect of anesthetics is greater on synaptic transmission than on axonal conduction. 22For this reason, responses recorded from polysynaptic pathways (e.g. , cortical recordings) are affected by anesthesia to a much greater extent than those recorded from oligosynaptic pathways (e.g. , spinal cord and subcortical recordings). 23For example, VEPs (which represent cortical activity) are very sensitive to the effects of anesthetics while BAEPs (representing brainstem and subcortical activities) are the least sensitive to drug effects.All volatile anesthetics produce a dose-dependent increase in SSEP latency, an increase in CCT, and a decrease in amplitude 23–29(table 1). They may also cause morphologic changes, such as contraction of early cortical waveforms (N-20) into a simple monophasic wave under deep isoflurane 30,31or sevoflurane 32,33anesthesia (fig. 4). The later cortical waveform components are most sensitive to volatile anesthetics, with marked attenuation at concentrations exceeding 0.5 minimum alveolar concentration (MAC). 30Satisfactory monitoring of early cortical SSEPs is possible with 0.5–1.0 MAC halothane, enflurane, or isoflurane without nitrous oxide. 24,26At 0.67 MAC halothane or less, SSEPs were recordable in 96% of cases but only in 91% with higher concentrations. 34During deep (1.6 MAC) isoflurane anesthesia, however, the early cortical N-20 wave was recordable 35in 94%, and amplitude decreased severely (table 1). 30Yet, the later N-35 wave, which is also important in IOM, could only be recorded in 47%. 35The effect of volatile anesthetics on cortical SSEP amplitude is compounded by nitrous oxide. Increasing isoflurane concentration from 0.5 to 1.0 MAC in the presence of nitrous oxide resulted in a 75% decrease in the cortical SSEP (from 1.2 μV to 0.3 μV). 36The newer volatile anesthetics desflurane and sevoflurane affect SSEPs not unlike isoflurane but may permit the use of higher inhaled concentrations (table 1). Increases in cortical latency and decreases in amplitude occur at doses of 1.5 MAC sevoflurane and desflurane or less, with minimal effects on subcortical SSEP components. 37,38Desflurane up to 1.0 MAC without nitrous oxide is compatible with cortical median nerve SSEP monitoring during scoliosis surgery. 38Even at 1.5 MAC (without nitrous oxide), the amplitude of cortical SSEPs was preserved at 60% of baseline. 39However, nitrous oxide added to desflurane 40or sevoflurane 41severely depresses amplitude. At 1.7–2.5 MAC sevoflurane, a high-amplitude early cortical SSEP waveform is found with absence of all later waves. 32,33How volatile anesthetics differ quantitatively in their effects on the SSEP is not completely settled. Pathak et al. 26showed that halothane had a greater effect on both amplitude and latency of the SSEP at equipotent concentrations than either isoflurane or enflurane. On the other hand, Peterson et al. 24found that isoflurane and enflurane reduced SSEP amplitude and prolonged CCT more than halothane did. Sevoflurane and desflurane are associated with less amplitude reduction than isoflurane at a MAC range of 0.7–1.3. 29In contrast to their effects on the cortical SSEP, all volatile anesthetics, even at concentrations above 1.0 MAC, only minimally affect the subcortical waveform, resulting in high recordability 35and reliability (table 2).Nitrous oxide (60–70%) generally diminishes cortical SSEP amplitude by approximately 50% while leaving cortical latency and subcortical waves unaffected. 36,42Nitrous oxide potentiates the depressant effect of volatile anesthetics 24,41and most intravenous anesthetics, 12,43,44producing greater amplitude depression than an equipotent concentration of volatile anesthetics administered alone 24,45,46(table 1). For example, adding 50% (0.5 MAC) nitrous oxide to a fentanyl-based anesthetic resulted in a greater decrease in amplitude than adding 1% (0.8 MAC) isoflurane, especially in patients with abnormal preoperative SSEP. 25Likewise, during opioid-based anesthetics, nitrous oxide depressed cortical SSEP amplitude to a greater extent than did propofol when substituted for nitrous oxide. 12,47–49Intravenous anesthetics generally affect SSEPs less than inhaled anesthetics (table 3). This is easily seen from the fact that the human SSEP is preserved even at high doses of narcotics and barbiturates (table 3) but abolished at high volatile anesthetic concentrations. Intravenous agents only modestly affect early and intermediate (&lt; 40 ms for median nerve stimulation and &lt; 80 ms for posterior tibial nerve stimulation) SSEP components. Low doses of intravenous agents have minimal effects on SSEPs, whereas high doses of most agents cause slight to moderate decreases in amplitude and increases in latency. With very few exceptions, subcortical potentials are unaffected (table 3).Barbiturates produce a dose-dependent increase in latency and decrease in early cortical SSEP amplitude that does not preclude IOM. Changes in long-latency cortical waves are affected more than subcortical and midlatency waveforms. This is consistent with the notion that barbiturates, like volatile anesthetics, affect synaptic transmission more than axonal conduction. An induction dose of thiopental (5 mg/kg) increases latency 10–20% and decreases amplitude 20–30%, an effect that lasts less than 10 min. 43,50,51Similar changes occur with thiamylal. 40Even at much higher doses, such as those used for barbiturate coma, barbiturates allow recording of cortical SSEPs. 52–55Unlike the barbiturates, etomidate dramatically increases cortical SSEP amplitude (N-20), up to 400% above preinduction baseline in some patients. 50,43Subcortical amplitude is decreased by up to 50% (table 3). 50,56Etomidate is associated with a high incidence of myoclonic movements. 57Patients with familial myoclonic epilepsy are also known to have abnormally large EPs, 58especially noted during myoclonic jerking episodes. It is tempting to speculate that myoclonus is an indication that sensory signals are being synchronized (pathologically or by etomidate), which then result in enhanced SSEP amplitude. However, Kochs et al. 59observed amplitude enhancement after etomidate whether or not myoclonic movements occurred. Based on careful electrophysiologic experiments in cats, SSEP amplitude enhancement with etomidate is thought to result from an altered balance between inhibitory and excitatory influences at the level of the cerebral cortex, 60resulting in increased signal synchronization at the thalamic level. 56Like etomidate, ketamine increases cortical SSEP amplitude, with the maximum effect occurring within 2–10 min of bolus administration. 61No effect on cortical latency 61or subcortical waveforms 62was evident. However, the addition of nitrous oxide 44or 1.0 MAC enflurane 61to a ketamine background anesthetic depressed SSEP amplitude by approximately 50%. Ketamine, 3 mg/kg, followed by 2 mg · kg−1· h−1combined with 0.15 mg · kg−1· h−1midazolam and 60% nitrous oxide was compatible with satisfactory recordings during major spine surgery. 63Propofol's effect on SSEPs is similar to that of the barbiturates. This is important because propofol can be infused in anesthetic concentrations during prolonged central nervous system (CNS) surgery and still effect rapid emergence for timely postoperative neurologic assessment. A dose of 2.5 mg/kg propofol produced no changes in the amplitude of the cortical (N-20) and subcortical (N-14) waves after median nerve stimulation. 62Cortical latency and CCT increased by 8 and 20%, respectively. In scoliosis surgery, total intravenous anesthesia with propofol and sufentanil (table 3) prolonged cortical latency 10–15% and reduced the amplitude of the cortical posterior tibial nerve SSEP by 50%. However, SSEP waveforms stabilized within 30 min after anesthetic administration and were compatible with IOM. 48When used as a sedative hypnotic in combination with opioids, propofol reduces SSEP amplitude less than nitrous oxide or midazolam. Cortical SSEP amplitude is approximately 50% lower during sufentanil–nitrous oxide 47,48or alfentanil–nitrous oxide anesthesia 49compared with sufentanil-propofol-opioid–based regimens. 47,48Propofol was associated with higher cortical SSEP amplitude despite the use of anesthetic concentrations equivalent to nitrous oxide or sevoflurane. 64Average cortical SSEP amplitude was higher and within-patient amplitude variability was less during propofol–alfentanil than during nitrous oxide–alfentanil anesthesia. 49Amplitude was also greater than during midazolam–alfentanil anesthesia. 65The typical W-shaped morphology of the cortical posterior tibial nerve SSEP was better preserved with propofol than with midazolam.Benzodiazepines have only mild-to-moderate depressant effects on SSEPs (table 3). Diazepam, 0.1–0.25 mg/kg, produced mild and moderate decreases in N-20 and later wave cortical amplitude, respectively. Very long latency peaks (200–400 ms) were abolished. 66In a dose of 0.2–0.3 mg/kg, midazolam is associated with modest 67or no 43reduction in amplitude and slight prolongation of median nerve SSEP latency (table 3). Adding opioids 43,68or nitrous oxide 43to midazolam or propofol 65preserves the cortical SSEP better when compared to adding nitrous oxide or opioids to thiopental, etomidate, 43or ketamine. 44Benzodiazepines affect sensory pathways differentially. The significant decrease in the amplitude of the evoked electromyelogram response (a spinal cord response to somatosensory stimulation) after diazepam 69indicates a peripheral action. Conversely, sedative doses of midazolam (60–70 μg/kg), while leaving the early cortical waveform (N-20) unaffected, depress late cortical waves generated in the association cortex. 69This is consistent with the notion that sedative doses of benzodiazepines might blunt the emotional response to pain perception. 70Most authors report clinically unimportant changes in SSEP latency and amplitude after the administration of opioids, whether given in analgesic or anesthetic doses (table 3).McPherson et al. 50found minimal SSEP changes after 25 μg/kg fentanyl for induction of anesthesia in adults. A small increase (5–6%) in cortical median nerve SSEP latency and a variable decrease (0–30%) in amplitude resulted after 36–71 μg/kg fentanyl, which was compatible with IOM. 71No significant effects on SSEP from fentanyl up to 130 μg/kg were observed during hypothermic cardiopulmonary bypass. The effect of fentanyl was greater with boluses compared to a continuous infusion 72during maintenance of anesthesia.A bolus dose of 5 μg/kg sufentanil produced 5% increases in early cortical SSEP latency and a 15% increase in CCT. 73The 40% decrease in cortical amplitude did not interfere with waveform acquisition. 73Sufentanil, 0.5–1.0 μg/kg, followed by 0.25–0.5 μg · kg−1· h−1with 50% nitrous oxide and 0.5% isoflurane prompted a 50% reduction in cortical amplitude and a 5–10% increase in cortical latency and CCT but no changes in subcortical waves. 74Alfentanil is associated with only modest SSEP amplitude depression while leaving latency unchanged 43,75(table 3). Three doses of remifentanil (table 3) combined with 0.4 MAC isoflurane produced a 20–30% decrease in early cortical amplitude that was not dose dependant. By contrast, late cortical waves showed a 10–30% increase in amplitude. 76Compared with the combination of fentanyl and nitrous oxide, remifentanil reduces cortical amplitude less, with lower amplitude variability. 77Pathak et al. 72reported posterior tibial nerve SSEP latency to increase by approximately 10–15% and amplitude to decrease by 20% after induction of anesthesia with 0.25 mg/kg morphine. Amplitude continued to decrease to approximately 10% of control during subsequent morphine infusion. This study could not isolate the effect of morphine from residual effects of the barbiturate used for induction and the effect of a background nitrous oxide anesthetic, but it shows that this regimen is not desirable for IOM. As with fentanyl, the magnitude of morphine's effect was greater with bolus administration than with continuous infusion.The administration of subarachnoid meperidine produced a 60% decrease in cortical posterior tibial nerve SSEP amplitude and a 10% increase in latency. The response was abolished in 40% of patients. 78This is attributed to the local anesthetic-like effect of meperidine in blocking voltage-dependent sodium channels. In contrast, subarachnoid fentanyl (25 μg), 78morphine (20 μg/kg) combined with sufentanil (50 μg), 79or morphine alone (15 μg/kg) 80produced no significant changes in latency or amplitude of cortical posterior tibial nerve SSEPS in the awake or anesthetized states, nor did the lumbar epidural administration of 0.1 mg/kg diamorphine in adolescents undergoing corrective surgery for idiopathic scoliosis. 81Droperidol is an acceptable anesthetic adjunct with minimal effects of SSEPs. 8Clonidine, an α2receptor agonist, reduces anesthetic requirements. 82,83However, clonidine administered alone 84or added to 1 MAC isoflurane 85did not change latency or amplitude of the cortical SSEP. At a dose of 10 μg/kg, subcortical amplitude decreased by 10%, and latency increased 2%. 86Clonidine can be used as an anesthetic without SSEP SSEP amplitude minimally at sedative isoflurane anesthesia, it effect on SSEP amplitude. patients undergoing spinal surgery, conditions for SSEP oxide anesthesia, does not affect human SSEPs. blocking drugs not influence SSEP, or they may waveform by the through of the electromyography at higher especially when EPs are at lower stimulation and higher local anesthetic of the sensory SSEPs. of the cortical evoked response to stimulation does subarachnoid the other hand, epidural administration of clonidine the SSEP on dose and The SSEP response to stimulation is abolished by epidural By contrast, because the nerve root is during epidural anesthesia, posterior tibial nerve stimulation can still an SSEP response. epidural anesthesia with was associated with decreased cortical amplitude and increased cortical SSEP latency, while 1% resulted in less into the lumbar epidural prolonged latency and decreased amplitude of posterior tibial nerve SSEPs, with only slight latency prolongation with administration of local anesthetics at higher concentrations is not to anesthesia in scoliosis surgery SSEPs are to be administered cortical SSEPs but is to interfere with IOM. administered at concentrations in patients anesthetized with sufentanil–nitrous dose (&lt; isoflurane further decreased amplitude of the cortical SSEP by approximately and produced a small latency of effects of anesthetics on waveform morphology and is reliable be for major anesthetic and anesthetic to assess the specificity and sensitivity of SEPs in the of neural injury to allow and much of the of anesthetic effects on SEPs were in patients or were obtained surgical on the nervous such as those presented in a for of the reliability of IOM in and neural injury during various to that an reproducible waveform (which to as during the anesthetic for to be with IOM. Anesthetic during which even a small of waveforms are not for IOM. are anesthetics that result in amplitude depression and latency prolongation on the that would the of SSEP changes and potentially either not detecting a or include volatile anesthetics alone at a dose greater than MAC and volatile anesthetics at greater than 0.5 MAC in combination with nitrous oxide (table 1). Therefore, volatile anesthetics alone at up to 1.0 MAC can be or sevoflurane may allow IOM at even higher intravenous anesthetic such as amplitude to be of (table 3). In however, intravenous anesthetic result in less amplitude and latency than volatile evoked potential waveform is to amplitude and to amplitude variability. the amplitude of the SSEP waveform, the more is it to baseline electrical and other confounding influences. Therefore, amplitude be one of the important of the intraoperative monitoring This is important when baseline amplitude is low and variability is as occurs in (&gt; patients and those with scoliosis, scoliosis, spinal spinal or other neurologic the negative between cortical SSEP amplitude and within-patient amplitude the possible SSEP amplitude be reduced cortical SSEP amplitude variability in patients undergoing spine surgery and amplitude. nitrous anesthesia, surgical stimulation may increase cortical amplitude by more than to amplitude variability. of propofol for nitrous oxide increases cortical SSEP amplitude by up to during an opioid-based nitrous oxide from the background anesthetic has been shown to cortical amplitude to IOM more of remifentanil for fentanyl and nitrous oxide during a isoflurane anesthetic also decreased SSEP waveform which nitrous oxide is to be used in in which amplitude to be it be used in combination with where it depresses amplitude the least with with or no effect on SSEPs, such as and opioids (table may also be effect allow lower doses of anesthetics to be with less depression of SSEP using agents known to increase the EP amplitude, such as etomidate or can be to use etomidate to IOM in patients with abnormally small SSEP waves due to preoperative administration of etomidate, mg/kg, followed by the infusion of mg · kg−1· waveforms and monitoring that would not have been increases in the amplitude of SSEP may represent an early of etomidate could interfere with early detection of et al. to detect intraoperative to spinal cord in patients in etomidate had been used to the SSEP that etomidate did not neural the volatile anesthetic concentration in an to IOM may be associated with Low concentrations of volatile anesthetics are used during IOM, and anesthesia may be to and consider using or that in the of anesthetic Adding etomidate or propofol is to nitrous oxide or volatile anesthetic concentrations when anesthetic is anesthetics are also used to control blood and and may to be substituted

The ventilatory response to hypoxia is composed of the stimulatory activity from peripheral chemoreceptors and a depressant effect from within the central nervous system. Morphine induces respiratory depression by affecting the peripheral and central carbon dioxide chemoreflex loops. There are only few reports on its effect on the hypoxic response. Thus the authors assessed the effect of morphine on the isocapnic ventilatory response to hypoxia in eight cats anesthetized with alpha-chloralose-urethan and on the ventilatory carbon dioxide sensitivities of the central and peripheral chemoreflex loops. The steady-state ventilatory responses to six levels of end-tidal oxygen tension (PO2) ranging from 375 to 45 mmHg were measured at constant end-tidal carbon dioxide tension (P[ET]CO2, 41 mmHg) before and after intravenous administration of morphine hydrochloride (0.15 mg/kg). Each oxygen response was fitted to an exponential function characterized by the hypoxic sensitivity and a shape parameter. The hypercapnic ventilatory responses, determined before and after administration of morphine hydrochloride, were separated into a slow central and a fast peripheral component characterized by a carbon dioxide sensitivity and a single offset B (apneic threshold). At constant P(ET)CO2, morphine decreased ventilation during hyperoxia from 1,260 +/- 140 ml/min to 530 +/- 110 ml/ min (P < 0.01). The hypoxic sensitivity and shape parameter did not differ from control. The ventilatory response to carbon dioxide was displaced to higher P(ET)CO2 levels, and the apneic threshold increased by 6 mmHg (P < 0.01). The central and peripheral carbon dioxide sensitivities decreased by about 30% (P < 0.01). Their ratio (peripheral carbon dioxide sensitivity:central carbon dioxide sensitivity) did not differ for the treatments (control = 0.165 +/- 0.105; morphine = 0.161 +/- 0.084). Morphine depresses ventilation at hyperoxia but does not depress the steady-state increase in ventilation due to hypoxia. The authors speculate that morphine reduces the central depressant effect of hypoxia and the peripheral carbon dioxide sensitivity at hyperoxia.

The effect of volatile anesthetics on cerebral blood flow depends on the balance between the indirect vasoconstrictive action secondary to flow-metabolism coupling and the agent's intrinsic vasodilatory action. This study compared the direct cerebral vasodilatory actions of 0.5 and 1.5 minimum alveolar concentration (MAC) sevoflurane and isoflurane during an propofol-induced isoelectric electroencephalogram. Twenty patients aged 20-62 yr with American Society of Anesthesiologists physical status I or II requiring general anesthesia for routine spinal surgery were recruited. In addition to routine monitoring, a transcranial Doppler ultrasound was used to measure blood flow velocity in the middle cerebral artery, and an electroencephalograph to measure brain electrical activity. Anesthesia was induced with propofol 2.5 mg/kg, fentanyl 2 micro/g/kg, and atracurium 0.5 mg/kg, and a propofol infusion was used to achieve electroencephalographic isoelectricity. End-tidal carbon dioxide, blood pressure, and temperature were maintained constant throughout the study period. Cerebral blood flow velocity, mean blood pressure, and heart rate were recorded after 20 min of isoelectric encephalogram. Patients were then assigned to receive either age-adjusted 0.5 MAC (0.8-1%) or 1.5 MAC (2.4-3%) end-tidal sevoflurane; or age-adjusted 0.5 MAC (0.5-0.7%) or 1.5 MAC (1.5-2%) end-tidal isoflurane. After 15 min of unchanged end-tidal concentration, the variables were measured again. The concentration of the inhalational agent was increased or decreased as appropriate, and all measurements were repeated again. All measurements were performed before the start of surgery. An infusion of 0.01% phenylephrine was used as necessary to maintain mean arterial pressure at baseline levels. Although both agents increased blood flow velocity in the middle cerebral artery at 0.5 and 1.5 MAC, this increase was significantly less during sevoflurane anesthesia (4+/-3 and 17+/-3% at 0.5 and 1.5 MAC sevoflurane; 19+/-3 and 72+/-9% at 0.5 and 1.5 MAC isoflurane [mean +/- SD]; P<0.05). All patients required phenylephrine (100-300 microg) to maintain mean arterial pressure within 20% of baseline during 1.5 MAC anesthesia. In common with other volatile anesthetic agents, sevoflurane has an intrinsic dose-dependent cerebral vasodilatory effect. However, this effect is less than that of isoflurane.

Volatile anesthetics can precondition the myocardium against functional depression and infarction following ischemia-reperfusion. Neutrophil activation, adherence, and release of superoxide play major roles in reperfusion injury. The authors tested the hypothesis that pretreatment of neutrophils with a volatile anesthetic, i.e., simulated preconditioning, can blunt their ability to cause cardiac dysfunction. Studies were performed in 60 buffer-perfused and paced isolated rat hearts. Left ventricular developed pressure served as an index of myocardial contractility. Polymorphonuclear neutrophils and/or drugs were added to coronary perfusate for 10 min, followed by 30 min of recovery. Platelet-activating factor was used to stimulate neutrophils. Pretreatment of neutrophils consisted of incubation with 1.0 minimum alveolar concentration (MAC) isoflurane or sevoflurane for 15 min, followed by washout. Additional studies were performed with 0.25 MAC isoflurane. Effects of superoxide dismutase were compared to those of volatile anesthetics. Superoxide production was measured by spectrophotometry. Neutrophil adherence to coronary vascular endothelium was estimated from the difference between neutrophils administered and recovered in coronary venous effluent. Activated neutrophils caused marked, persistent reduction (> 50%) in left ventricular developed pressure. Isoflurane and sevoflurane at 1.0 MAC and superoxide dismutase abolished this effect. Isoflurane and sevoflurane reduced superoxide production of activated neutrophils by 29% and 33%, respectively, and completely prevented the platelet-activating factor-induced increases in neutrophil adherence. Isoflurane at 0.25 MAC blunted, but did not abolish, the neutrophil-induced decreases in left ventricular developed pressure. Neutrophils pretreated with 1.0 MAC isoflurane or sevoflurane lost their ability to cause cardiac dysfunction, while those pretreated with a concentration of isoflurane as low as 0.25 MAC were partially inhibited. This action of the volatile anesthetics was associated with reductions in superoxide production and neutrophil adherence to the coronary vascular endothelium. Our findings suggest that inhibitory actions on neutrophil activation and neutrophil-endothelium interaction may contribute to the preconditioning effects of volatile anesthetics observed in vivo during myocardial ischemia-reperfusion.

Characteristics of the relationship between plasma ketamine concentration and its effect on the minimum alveolar concentration of isoflurane in dogs

The effect of epidural morphine on the minimum alveolar concentration of isoflurane in cats

This study was carried out to compare the cerebral and systemic circulatory effect of halothane and isoflurane. Six mongrel dogs were anesthetized with 1.3 minimal alveolar concentration (MAC) (1%) halothane and were compared with six mongrel dogs anesthetized with 1.3 MAC (1.5%) isoflurane. Likewise, 6 dogs anesthetized with 1.7 MAC (1.3%) halothane were compared with 6 dogs anesthetized with 1.7 MAC (2%) isoflurane. Blood flow (using the radioactive microsphere technique) and cardiovascular measurements were obtained 2 hours after the induction of anesthesia and were repeated 5 more times at hourly intervals. The heart rate was similar in all groups of dogs, except that it was significantly lower with 1.7 MAC halothane. The mean arterial pressure was statistically higher with isoflurane at both concentrations than with halothane. The cardiac index was similar in all groups, except with 1.7 MAC isoflurane, when it was higher. At the early measurements, total cerebral blood flow (CBF) was above “normal” levels in all groups. At 1.3 MAC, the total CBF tended to be lower with isoflurane, but did not reach statistically significant levels. Blood flow decreased over time in all groups. The cerebral vascular resistance (CVR) mirrored the changes in blood flow, showing no difference between agents at 1.7 MAC, but the CVR with isoflurane was significantly higher at 1.3 MAC than it was with halothane. Regional cerebral blood flow showed marked differences. Regional flow to the hemispheres and the cortical gray matter showed that isoflurane tended to produce lower blood flow, particularly at the 1.3 MAC concentration. The reverse was true in the posterior fossa structures, with the brain stem and cerebellum showing higher blood flows with isoflurane, particularly at 1.7 MAC. Isoflurane may have several advantages over halothane for neurosurgical procedures. (Neurosurgery 15:400-409, 1984)

This study was carried out to compare the cerebral and systemic circulatory effect of halothane and isoflurane. Six mongrel dogs were anesthetized with 1.3 minimal alveolar concentration (MAC) (1%) halothane and were compared with six mongrel dogs anesthetized with 1.3 MAC (1.5%) isoflurane. Likewise, 6 dogs anesthetized with 1.7 MAC (1.3%) halothane were compared with 6 dogs anesthetized with 1.7 MAC (2%) isoflurane. Blood flow (using the radioactive microsphere technique) and cardiovascular measurements were obtained 2 hours after the induction of anesthesia and were repeated 5 more times at hourly intervals. The heart rate was similar in all groups of dogs, except that it was significantly lower with 1.7 MAC halothane. The mean arterial pressure was statistically higher with isoflurane at both concentrations than with halothane. The cardiac index was similar in all groups, except with 1.7 MAC isoflurane, when it was higher. At the early measurements, total cerebral blood flow (CBF) was above "normal" levels in all groups. At 1.3 MAC, the total CBF tended to be lower with isoflurane, but did not reach statistically significant levels. Blood flow decreased over time in all groups. The cerebral vascular resistance (CVR) mirrored the changes in blood flow, showing no difference between agents at 1.7 MAC, but the CVR with isoflurane was significantly higher at 1.3 MAC than it was with halothane. Regional cerebral blood flow showed marked differences. Regional flow to the hemispheres and the cortical gray matter showed that isoflurane tended to produce lower blood flow, particularly at the 1.3 MAC concentration. The reverse was true in the posterior fossa structures, with the brain stem and cerebellum showing higher blood flows with isoflurane, particularly at 1.7 MAC. Isoflurane may have several advantages over halothane for neurosurgical procedures.