Jan H. Baars

Monitoring of Immobility to Noxious Stimulation during Sevoflurane Anesthesia Using the Spinal H-reflex

BackgroundThe spinal H-reflex has been shown to correlate with surgical immobility, i.e., the absence of motor responses to noxious stimulation, during isoflurane anesthesia. Here, the authors established individual concentration–response functions for H-reflex amplitude and tested the predictive power of the H-reflex for movement responses during sevoflurane anesthesia in comparison to electroencephalographic parameters. In addition, they investigated the effect of noxious stimulation on the H-reflex itself. MethodsThe authors studied 12 female patients during sevoflurane anesthesia before surgery. The sevoflurane concentration was increased, a laryngeal mask was inserted, and then the sevoflurane concentration was decreased until H-reflex amplitude (recorded over the soleus muscle) recovered. Thereafter, the end-tidal sevoflurane concentration was kept at a constant value close to the minimum alveolar concentration for suppression of movement responses after tetanic stimulation (MACtetanus), determined by the Dixon up–down method. Pharmacodynamic modeling of H-reflex amplitude and of the Bispectral Index was performed, and predictive values for motor responses to noxious electrical stimulation (50 Hz, 60 mA tetanus, volar forearm) were compared using the prediction probability. ResultsConcentration-dependent depression of H-reflex amplitude by sevoflurane was well modeled (median r2 = 0.97) by a sigmoid function with a median EC50 of 1.5 vol% and a median slope parameter of 3.7, much steeper than the slope for the Bispectral Index. MACtetanus calculated by logistic regression was 1.6 vol%. H-reflex amplitude predicted motor responses to noxious stimulation with a prediction probability of 0.76, whereas the prediction probability for Bispectral Index and spectral edge frequency (SEF95) were not different from chance alone. Noxious stimulation was followed by a substantial increase of H-reflex amplitude for several minutes, whereas the Bispectral Index and SEF95 exhibited no significant changes. ConclusionsSuppression of movement to noxious stimulation and suppression of H-reflex amplitude by sevoflurane follow similar concentration–response functions. Although this does not imply a causal relation, it explains the high predictive value of H-reflex amplitude for motor responses to noxious stimuli, even in a narrow concentration range around the MACtetanus.

Monitoring of the responsiveness to noxious stimuli during anaesthesia with propofol and remifentanil by using RIII reflex threshold and bispectral index

BACKGROUND Movement responses are an important indicator of noxious perception in the unconscious state. To allow for a continual monitoring of the responsiveness to noxious stimuli during general anaesthesia, surrogate parameters are needed. Here we compare the performance of the bispectral index (BIS) and the RIII threshold in predicting reactions to noxious stimuli during anaesthesia with propofol and remifentanil. METHODS Twenty male volunteers were included. The first 10 subjects received constant concentrations of propofol while remifentanil concentrations were increased stepwise. The other 10 subjects each received high propofol concentrations combined with different low remifentanil concentrations and also low propofol concentrations combined with different high remifentanil concentrations. In all subjects, the reactions to an 80 mA 30 s tetanic stimulus were tested every 5 min. BIS and RIII threshold were recorded continually in all subjects. RESULTS Nineteen subjects completed the study. The population prediction probability for reactions to the noxious stimuli amounted to 0.86 for the BIS and to 0.84 for the RIII threshold in the first 10 subjects (P>0.05, PKDMACRO). In the other nine subjects, the prediction probabilities amounted to 0.64 for the BIS and to 0.77 for the RIII threshold (P<0.05, PKDMACRO). All population prediction probability values differed significantly from 0.5 (P<0.01, PKDMACRO). CONCLUSIONS RIII threshold and BIS are both influenced dose-dependently by remifentanil at those concentrations that suppress reactions to noxious stimuli. The susceptibility of the parameters to remifentanil concentration seems to be of a similar quality. Under different ratios of propofol and remifentanil concentrations, the RIII threshold correlates with non-responsiveness better than the BIS.

Utility of Nociceptive Flexion Reflex Threshold, Bispectral Index, Composite Variability Index and Noxious Stimulation Response Index as measures for nociception during general anaesthesia

Movement and haemodynamic responses to noxious stimuli during general anaesthesia are regarded as signs of nociception. We compared the Nociceptive Flexion Reflex Threshold (NFRT), Bispectral Index (BIS), Composite Variability Index (CVI), Noxious Stimulation Response Index (NSRI) and the calculated propofol/remifentanil effect‐compartment concentrations (Ce) as predictors for such responses in 50 female subjects at laryngeal mask airway insertion and skin incision. The following prediction probabilities (PK‐values) were obtained at laryngeal mask airway insertion and skin incision, respectively. For movement responses: NFRT = 0.77 and 0.72; p = 0.0001 and 0.004, respectively; BIS = 0.41 and 0.56, p = 0.29 and 0.5, respectively; CVI = 0.48 and 0.57, p = 0.76 and 0.88, respectively; NSRI = 0.49 and 0.76, p = 0.92 and 0.0001, respectively; propofol‐Ce = 0.35 and 0.66, p = 0.04 and 0.03, respectively; remifentanil‐Ce = 0.68 and 0.72, p = 0.01 and 0.003, respectively. For heart rate responses: NFRT = 0.68 and 0.75, p = 0.04 and 0.01, respectively; BIS = 0.37 and 0.59, p = 0.15 and 0.41, respectively; CVI = 0.41 and 0.44, p = 0.39 and 0.37, respectively; NSRI = 0.48 and 0.53, p = 0.84 and 0.78, respectively; propofol‐Ce = 0.42 and 0.56, p = 0.39 and 0.53, respectively; remifentanil‐Ce = 0.58 and 0.54, p = 0.35 and 0.73, respectively. We conclude that the NFRT best predicts movement and heart rate responses to noxious stimuli. Effect‐compartment concentrations and NSRI also predict movement (but not heart rate) responses satisfactorily.

Comparison of the nociceptive flexion reflex threshold and the bispectral index as monitors of movement responses to noxious stimuli under propofol mono-anaesthesia

BACKGROUND Prediction of movement responses to noxious stimuli during anaesthesia is of clinical importance. Susceptibility of a parameter of immobility to both hypnotic and analgesic influences could pose an advantage. Here, nociceptive reflexes might be useful, but data regarding the suppression by hypnotic substances are scarce. Therefore, we compared the prediction of movement responses by the RIII reflex threshold and the bispectral index (BIS) during propofol mono-anaesthesia. METHODS Fifteen male volunteers were included. Propofol effect compartment concentration was increased every 15 min in steps of 1 microg ml(-1) (max 7 microg ml(-1)). Every 5 min, the reactions to trapezius squeezes and 30 s tetanic stimulations (80 mA) of the right ulnar nerve were tested. The RIII reflex threshold was estimated continuously using an automated threshold tracking system that analyses the nociceptive RIII response at the left biceps femoris muscle to stimulation of the left sural nerve. RESULTS Twelve subjects completed the study. RIII threshold values were normalized by subtraction of the first threshold that was estimated after the subjects loss of consciousness. The population prediction probability P(K) amounted to 0.84 for the RIII threshold and to 0.86 for the BIS (difference not significant). CONCLUSIONS Movement responses to noxious stimuli under propofol can be predicted by the RIII threshold with a comparable accuracy as the BIS. Therefore, the RIII threshold seems to be influenced by hypnotic effects. Since susceptibility of the RIII threshold to analgesic influences is well established, an advantage for the RIII threshold in the prediction of motor responses could be expected when analgesic substances are used in addition to propofol.

Introduction of a continual RIII reflex threshold tracking algorithm

INTRODUCTION The RIII reflex is used in fundamental and clinical pain research. Here we introduce a continual reflex threshold tracking algorithm to facilitate investigations of the time courses of influences on the threshold. METHODS First we investigated the probability of reflex occurrence at the threshold estimated by the continual algorithm and the changes of the threshold over the time during continual recordings of 100 min duration in 10 subjects. Secondly we compared the threshold estimates of the continual algorithm with those of a standard algorithm of threshold estimation in 52 subjects and compared the differences between the two methods with the test-retest-variability of each method. RESULTS The average probability of reflex occurrence at the threshold estimated by the continual algorithm was 48.7% (SD = 3.2%). Changes of the RIII reflex threshold over the time were not significant (Friedman test, p>0.05). The variability between the thresholds determined by the different algorithms (test: SD = 2.50 mA, retest: SD = 1.80 mA) was lower than the variability between test and retest (standard algorithm: SD = 4.32 mA, continual algorithm: SD = 4.44 mA). DISCUSSION The continual algorithm can be used for a continuous estimation of the reflex threshold at the 50% probability of reflex-occurrence. No evidence of habituation was detected. This allows for investigations of the time courses of pharmacological and physiological influences on the reflex threshold by using this algorithm. The lower variability between the continual algorithm and the standard algorithm compared to the variability between tests and retests of the methods allows for interchangeable conclusions drawn from data obtained with both methods.

Effects of Sevoflurane and Propofol on the Nociceptive Withdrawal Reflex and on the H Reflex

Background:The predominant target of anesthetics to suppress movement responses to noxious stimuli is located in the spinal cord. Although volatile anesthetics appear to produce immobility by actions on the ventral rather than the dorsal horn, the site of action of propofol remains unclear. Methods:In a crossover design, the authors compared in 13 volunteers the effects of sevoflurane and propofol on the amplitudes of the H reflex, which is mediated exclusively in the ventral horn and a withdrawal reflex (RIII Reflex), which integrates dorsal and ventral horn function. The concentrations were adjusted according to a Dixon up-and-down approach, depending on movement responses to tetanic stimulation. Results:Sevoflurane and propofol concentrations ranged from 1.2 to 1.6 Vol% and 3 to 6 mg/l, respectively. Sevoflurane reduced the H reflex amplitude significantly to 66 ± 17% (mean ± SD) of its control values. Propofol did not significantly reduce the H reflex. The reductions under the two drugs differed significantly. The RIII reflex amplitude was significantly reduced to 19 ± 10% and 27 ± 12% (mean ± SD) of the control values by sevoflurane and propofol, respectively. The reductions did not differ between the drugs. Conclusions:Probably because of the polysynaptic relay, the attenuation of the withdrawal reflex exceeds the attenuation of the H reflex. Sevoflurane produces a larger inhibitory effect on the H reflex than propofol, which confirms that the ventral horn is a more important target for volatile anesthetics, whereas effects of propofol on this site of action are rather limited. Our findings indirectly suggest for propofol a relatively stronger effect within the dorsal horn.

Suppression of the human spinal H-reflex by propofol: a quantitative analysis

Background:  The spinal cord is an important site of anaesthetic action because it mediates surgical immobility. During anaesthesia with volatile anaesthetics, it has been shown that the suppression of the spinal H‐reflex correlates with surgical immobility. To evaluate whether the H‐reflex could also be a possible candidate for monitoring immobility during propofol anaesthesia, this study assessed the concentration‐dependent suppression of the H‐reflex by propofol. To discriminate different effect sites, the individual concentration response‐curves and the t1/2ke0 of the H‐reflex have been compared with those of two EEG parameters.

Monitoring of the responsiveness to noxious stimuli during sevoflurane mono-anaesthesia by using RIII reflex threshold and bispectral index

BACKGROUND We investigated the accuracy of the (normalized) RIII reflex threshold, the bispectral index (BIS), and the end-tidal sevoflurane concentration for predicting movement responses during mono-anaesthesia using sevoflurane. METHODS Fourteen male subjects were included. Each received a sevoflurane mono-anaesthesia for which the end-tidal concentration was increased in steps of 0.2 vol% every 10 min. Every 5 min, the reactions to noxious stimuli (10 s trapezius squeeze and 30 s 80 mA tetanic stimulus) were tested. The administration of sevoflurane was halted after no movement reactions occurred for three concentration steps. RIII reflex threshold and BIS were recorded continually in all subjects. RESULTS Thirteen subjects completed the study. The prediction probabilities for movement reactions to the noxious stimuli were 0.79 for the BIS, 0.91 for the RIII threshold, and 0.89 for the end-tidal sevoflurane concentration (PKDMACRO-Statistics: BIS vs RIII, P<0.05; BIS vs C(sevo), P<0.05; RIII vs C(sevo), P>0.05). All population prediction probability values differed significantly from 0.5 (P<0.01, PKDMACRO). CONCLUSIONS All three instruments can be used for a prediction of movement responses to a noxious stimulus under sevoflurane mono-anaesthesia with an accuracy exceeding prediction by chance. The accuracy of the BIS to predict these responses appears to be lower compared with the RIII reflex threshold or the end-tidal sevoflurane concentration.

Variability Comparison of the Composite Auditory Evoked Potential Index and the Bispectral Index During Propofol-fentanyl Anesthesia

BACKGROUND: Monitors of hypnotic depth help anesthesiologists to guide the anesthetic. The performance of different monitors depends on several factors, index variability at a steady state of hypnotic depth being one. We compared the recently introduced AAI1.6 with the established bispectral index (BIS), regarding index variability during stable values of propofol effect-site concentration. METHODS: After ethics committee approval and written informed consent, anesthesia was performed in 40 patients with propofol as the target controlled infusion and fentanyl. Variability of BIS and AAI1.6 was calculated during periods of constant predicted propofol effect compartment concentration and constant levels of surgical stimulation as the median absolute deviation (MAD) from the median value. A variability index was calculated as 1.48*MAD/(threshold − median value), with threshold being the division line between awake and asleep. Threshold crossing time was used to evaluate the performance in predicting return of consciousness. RESULTS: Variability index, however, was significantly larger for the AAI1.6, despite similar absolute variability measured as MAD. Lightening of anesthesia before recovery could be noticed earlier using the BIS than the AAI1.6, although consciousness was detected with a significantly higher Pk-value by the AAI1.6. CONCLUSION: Variability in relation to the difference between the median index value during anesthesia and the threshold necessary to detect consciousness with high sensitivity is higher for the AAI1.6 than for the BIS. This, as well as the steeper concentration–response function found for AAI1.6, impairs the performance of the AAI1.6 in predicting imminent return of consciousness during decreasing propofol concentrations. However, it makes AAI1.6 well suited to detect consciousness when it has occurred.

Comparison of a new composite index based on midlatency auditory evoked potentials and electroencephalographic parameters with bispectral index (BIS) during moderate propofol sedation

Background and objective: Derived parameters of the electroencephalogram and auditory evoked potentials can be used to determine depth of anaesthesia and sedation. However, it is not known whether any parameter can identify the occurrence of awareness in individual patients. We have compared the performance of bispectral index and a new composite index derived from auditory evoked potentials and the electroencephalogram (AAI 1.61) in predicting consciousness, explicit and implicit memory during moderate sedation with propofol. Methods: Twenty‐one patients with spinal anaesthesia received intraoperatively propofol at the age‐corrected C50 for loss of consciousness and were presented test words via headphones. Bispectral index and AAI 1.61 (auditory evoked potentials, AEP‐Monitor2) were recorded in parallel as well as the Observers Assessment of Alertness/Sedation‐score. Postoperatively, testing for explicit and implicit memory formation was performed. Results: Bispectral index and AAI 1.61 correlated well with loss of consciousness defined by an Observers Assessment of Alertness/Sedation‐score of 2 (identical PK of 0.87), but did not allow a prediction of postoperative explicit or implicit recall. Conclusions: Both bispectral index and AAI may be indices of depth of sedation rather than indicators of memory formation, which persists during propofol sedation even after loss of consciousness.