B. Rehberg

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.

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.

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.

Use of a target-controlled infusion system for propofol does not improve subjective assessment of anaesthetic depth by inexperienced anaesthesiologists

Background and objectives: Target‐controlled infusion, via the calculated effect compartment concentrations, may help anaesthesiologists to titrate anaesthetic depth and to shorten recovery from anaesthesia. Methods: In this prospective, randomized clinical study, we compared the performance of six inexperienced anaesthesiologists with <1 yr of training when using target‐ or manually controlled infusion of propofol, combined with manual dosing of fentanyl. Ninety‐two premedicated ASA I‐III patients undergoing minor elective urological or gynaecological surgery were assigned to the manual‐ or target‐controlled infusion group. Bispectral index was recorded in a blinded manner. Subjective assessment of anaesthetic depth on a 10 point numerical scale (1 = very deep anaesthesia, 10 = awake) was asked at regular intervals and the correlation with the blinded bispectral index was analysed using the prediction probability, PK. The propofol concentration profile was calculated post hoc. Results: Propofol administration was similar in both groups with no significant difference for the administered amount and concentrations of propofol. Recovery times were also not different. In both groups, a large percentage of the bispectral index data points recorded during surgery showed bispectral index values below the recommended value of 40, but in the target‐controlled infusion group there were significantly less bispectral index values above the recommended upper limit of 60 (2.5% vs. 5.1%). Conclusions: A target‐controlled infusion system does not help inexperienced anaesthesiologists to assess anaesthetic depth or to shorten recovery times, but may reduce episodes of overly light anaesthesia and thus help to prevent awareness.

Ethanol reduces motoneuronal excitability and increases presynaptic inhibition of Ia afferents in the human spinal cord.

INTRODUCTION Already low blood concentrations of ethanol acutely impair motor control and coordination. In vitro experiments have given evidence that spinal effects of ethanol contribute to this by reducing spinal excitability and enhancing presynaptic inhibition of Ia fibers. In this study, we investigated the influence of 0.7 g per kilogram of bodyweight ethanol on motoneuronal excitability and presynaptic inhibition in humans. METHODS The study was performed in 10 volunteers. Spinal excitability was measured by the maximal H-reflex of the soleus muscle normalized to the maximal muscular response (Hmax/Mmax). Presynaptic inhibition was measured by changes in heteronymous Ia-facilitation of the soleus H-reflex, which is achieved by stimulation of the femoral nerve. A decrease in facilitation can be ascribed to an increase in presynaptic inhibition. Changes of these parameters under the influence of 0.7 g per kilogram of bodyweight ethanol were assessed in comparison to control measurements before ethanol application. RESULTS Both parameters, Hmax/Mmax and Heteronymous facilitation, were significantly reduced under the influence of ethanol (Wilcoxon signed-rank test with Bonferroni correction for each, p<0.01). DISCUSSION The increase in presynaptic inhibition by ethanol is probably caused by an increase in GABAA receptor-mediated Cl-conductance, which has been shown in spinal cord cultures. The role of presynaptic inhibition in movement is assumed to be there to control the afferent input of muscle spindles and tendon organs as a mechanism of specific input-selection. This study demonstrated that ethanol reduces spinal excitability and increases GABAergic presynaptic inhibition on Ia afferent fibers in humans.

subjective assessment of depth of anaesthesia by experienced and inexperienced anaesthetists

Background and objective: To measure ‘depth of anaesthesia’, anaesthesiologists use a combination of observable end‐points such as immobility and autonomic stability. Unconsciousness and amnesia are not reliably observable end‐points, but correlate with parameters derived from the electroencephalogram. We investigated the association of subjective assessment and electroencephalographic measures of anaesthetic depth in a group of experienced (>4 yr of experience) and a group of inexperienced (<2 yr of experience) anaesthesiologists. Methods: One hundred ASA I or II patients were assigned to either group. Anaesthesiologists assessed ‘anaesthetic depth’ using an 11‐point numeric and a 5‐point verbal scale. Bispectral index and spectral entropy were recorded as electroencephalogram parameters. The association between the subjective assessment and the electroencephalogram parameters was calculated using the prediction probability, PK. Results: Association between subjective assessment and electroencephalographic parameters showed a tendency to a better prediction probability in the experienced group. The difference was significant (P < 0.05) for the bispectral index (PK 0.76 ± 0.01 for experienced and 0.71 ± 0.01 for inexperienced anaesthesiologists). In both groups, a large percentage of the data points recorded during surgery showed bispectral index values above the recommended value of 60 (13.2% in the experienced and 34.3% in the inexperienced group) despite a subjective assessment of ‘deep’ or ‘very deep’ anaesthetic depth. Conclusion: The study demonstrates that the association between subjectively assigned values of anaesthetic depth and electroencephalographic parameters of anaesthetic depth is better for anaesthesiologists with more clinical experience. However, in the ‘inexperienced’ as well as ‘experienced’ group a high percentage of bispectral index and entropy values above 60 occurred despite a subjective assessment of adequate anaesthetic depth. Although there was no evidence for explicit memory, this may indicate a risk for memory formation.