Performance of Surgical Stress Index during Sevoflurane-Fentanyl and Isoflurane-Fentanyl Anesthesia.

The performance of recently introduced Surgical Stress Index (SSI), based on heart rate and photoplethysmography, was estimated during sevoflurane-fentanyl and isoflurane-fentanyl anesthesia during surgical procedures. Forty ASA I-III patients were enrolled. Anesthesia was induced with fentanyl 2 mug kg(-1) and thiopentone 3-5 mg kg(-1). Tracheal intubation was performed 5 minutes after fentanyl bolus. Patients were randomly allocated to receive sevoflurane (n = 20) or isoflurane (n = 20) in 30% oxygen/air. State entropy was kept at 40-60, target being 50. During surgery, fentanyl boluses 1.5 mug kg(-1) were given at 30-40-minute intervals. SSI increased significantly after intubation. During surgery, the decrease of SSI after fentanyl boluses was similar in sevoflurane and isoflurane groups but SSI values were higher in sevoflurane than in isoflurane group. Tracheal intubation, skin incision, and surgical stimuli increased SSI from baseline, indicating that nociceptive stimuli increase SSI. Fentanyl boluses during surgery decreased SSI, indicating that increasing analgesia decreases SSI.

Effects of nitric oxide synthase inhibition on dexmedetomidine-induced vasoconstriction in healthy human volunteers.

BACKGROUND: This study aimed to assess the contribution of endothelial nitric oxide synthesis to the net responses of human peripheral blood vessels in vivo to the selective alpha(2)-adrenoceptor agonist dexmedetomidine. METHODS: Two groups of healthy young men were studied. In the first experiment, after brachial plexus block, the responses of digital arteries to systemically administered dexmedetomidine (target plasma concentration 1.2 ng ml(-1)) were studied using a photoplethysmograph (n=10) during i.a. infusions of saline and the nitric oxide synthase (NOS) inhibitor N(G)-monomethyl-L-arginine (L-NMMA) (8 micromol min(-1)). In a separate experiment, after pre-treatment with acetylsalicylic acid, responses to increasing doses of dexmedetomidine (0.01-164 ng min(-1)) in the presence and absence of L-NMMA were compared in dorsal hand veins (DHV) (n=10) using linear variable differential transformers. RESULTS: L-NMMA significantly augmented dexmedetomidine-induced vasoconstriction of digital arteries as assessed by an increase in light transmission through a finger and by a decrease in finger temperature. The mean (95% confidence interval) extent of the additional effect of L-NMMA over the constrictor effect of dexmedetomidine alone was 19% (14-24) (P<0.0001). In DHV, L-NMMA had variable effects on the dexmedetomidine-constriction dose-response curve. In three subjects, the curve was shifted significantly to the left (with a >10-fold difference in ED(50)), but ED(50) was only marginally affected by L-NMMA in the other subjects (difference in ED(50)

Surgical stress index as a measure of nociception/antinociception balance during general anesthesia.

BACKGROUND: No validated monitoring method is available for evaluating the nociception/antinociception balance. We assessed the surgical stress index (SSI), computed from finger photoplethysmographic waveform amplitudes and pulse-to-pulse intervals, in patients undergoing shoulder surgery under general anesthesia (GA) and interscalene plexus block and in patients with GA only. METHODS: In this prospective, randomized study in 26 patients, increased blood pressure (BP) or heart rate, movement, and coughing were considered to be signs of intraoperative nociception and were treated with alfentanil. GA was maintained with desflurane aiming at a State Entropy level of 50. Photoplethysmographic waveforms were collected from the contra-lateral arm to the surgery and SSI values from 0 (no surgical stress) to 100 (maximal surgical stress) were calculated off-line. RESULTS: Two minutes after skin incision, SSI had not increased in the plexus group and was lower in the plexus group (38 +/- 13) compared with the controls (58 +/- 13, P<0.005). Among the controls, 1 min before alfentanil administration, the SSI value was higher than during periods of adequate antinociception, 59 +/- 11 vs. 39 +/- 12 (P<0.01). The total cumulative need for alfentanil was higher in controls (2.7 +/- 1.2 mg) compared with the plexus group (1.6 +/- 0.5 mg; P=0.008). Tetanic stimulation to the ulnar region of the hand increased SSI significantly only among the patients with plexus block not covering the site of the stimulation. CONCLUSION: SSI values were lower in patients with plexus block covering the sites of nociceptive stimuli. In detecting nociceptive stimuli, SSI had better performance than heart rate, BP, or response entropy.

Changes in a surgical stress index in response to standardized pain stimuli during propofol-remifentanil infusion.

BACKGROUND: The surgical stress index (SSI) is based on a sum of the normalized pulse beat interval (PBI) and the pulse wave amplitude (PPGA) time series of the photoplethysmography. As a measure of the nociception-anti-nociception balance in response to a standardized pain stimulus, SSI was compared with EEG changes in state and response entropy (SE and RE), PPGA, and heart rate (HR) during various targeted pseudo-steady-state concentrations of propofol and remifentanil. METHODS: Forty ASA I patients were allocated to one of the four groups to receive a remifentanil step-up/-down effect-compartment target-controlled infusion (Ce(remi)) of 0, 2, 6, 2, 0 ng ml(-1), or 6, 2, 0, 2, 6 ng ml(-1), and an effect-compartment target-controlled propofol infusion (Ce(prop)) to keep the SE between 30 and 50 or 15 and 30, respectively. At each steady-state Ce(remi), maximum change in SSI, SE, RE, PPGA, and HR after a noxious stimulus was compared with the baseline value. A correlation and prediction probability (P(K)) with Ce(prop) and Ce(remi) was measured. RESULTS: Static and dynamic values of SSI correlated to Ce(remi) better than SE, RE, HR, and PPGA. SSI was independent of Ce(prop), in contrast to SE and RE. The P(K) for Ce(remi) both before and during a noxious stimulus was better with SSI. CONCLUSIONS: SSI appeared to be a better measure of nociception-anti-nociception balance than SE, RE, HR, or PPGA.

Tetanic stimulus of ulnar nerve as a predictor of heart rate response to skin incision in propofol remifentanil anaesthesia.

BACKGROUND: To study adequate antinociception during general anaesthesia, tetanic stimulus of 5-10 s duration has been used previously as a standardized nociceptive stimulus. However, such stimuli have been found to correlate poorly with intraoperative nociception. We hypothesized that an electrical tetanic stimulus of the ulnar nerve, lasting 30 s, would provide a reliable experimental pain model. METHODS: Thirty-three patients, undergoing open abdominal surgery, were studied. Propofol and remifentanil were used for anaesthesia. Patients were randomized to receive remifentanil at three target-controlled infusion levels (1, 3, or 5 ng ml(-1)) during short (5 s, Tet5) and a long-lasting (30 s, Tet30) tetanic (50 mA, 50 Hz) stimulus and skin incision. RR intervals (RRI) were obtained from the ECG and the mean RRI before each stimulus (Tet5, Tet30, incision) was compared with that after the stimulus. RESULTS: At remifentanil level 1 ng ml(-1), the RRI responses to tetanic stimuli and skin incision were prominent but with higher concentrations (3 and 5 mg ml(-1)), responses were very small. Tet30 (r(2)=0.780) was the best predictor of the RRI response to skin incision when compared with Tet5 (r(2)=0.611), remifentanil level (r(2)=0.340), or propofol level (r(2)=0.036). CONCLUSIONS: Long-lasting tetanic stimulus of ulnar nerve may provide a better experimental pain model for surgical pain during general anaesthesia than shorter stimuli, which have been applied in earlier studies.

Surgical stress index reflects surgical stress in gynaecological laparoscopic day-case surgery.

BACKGROUND: Monitoring of analgesia remains a challenge during general anaesthesia. The surgical stress index (SSI) is derived from the photoplethysmographic waveform amplitude and the heart beat-to-beat interval. We evaluated the ability of SSI to measure surgical stress in patients undergoing gynaecological laparoscopy. Our hypothesis was that while keeping State Entropy (SE) at a predetermined level, SSI would be higher in patients receiving a beta-blocking agent (esmolol) than in those receiving an opioid (remifentanil) during laparoscopy. METHODS: Thirty women undergoing gynaecological laparoscopy were assigned randomly to receive esmolol (n = 15) or remifentanil (n = 15). Anaesthesia was induced with propofol and fentanyl and maintained with desflurane and nitrous oxide 50% in oxygen to keep SE at 50(5). The infusion of esmolol or remifentanil was started before laparoscopy and adjusted to keep the systolic blood pressure at -20 to +10% from the preoperative value. RESULTS: During the fentanyl phase, before surgery, both groups behaved similarly, with an increase in SSI after intubation. In the patients receiving esmolol, the SSI reacted to the initial incision (P < 0.05), and remained high after trocar insertion (P < 0.05). In patients receiving remifentanil, it did not react to the initial incision, but increased after trocar insertion (P < 0.05), and it remained lower both after incision (P < 0.05) and after trocar insertion (P < 0.05). CONCLUSION: SSI was higher in patients receiving esmolol. The index seems to reflect the level of surgical stress and may help guide the use of opioids during general anaesthesia.

Assessment of surgical stress during general anaesthesia.

BACKGROUND: Inadequate analgesia during general anaesthesia may present as undesirable haemodynamic responses. No objective measures of the adequacy of analgesia exist. We aimed at developing a simple numerical measure of the level of surgical stress in an anaesthetized patient. METHODS: Sixty and 12 female patients were included in the development and validation data sets, respectively. All patients had elective surgery with propofol-remifentanil target controlled anaesthesia. Finger photoplethysmography and electrocardiography waveforms were recorded throughout anaesthesia and various waveform parameters were extracted off-line. Total surgical stress (TSS) for a patient was estimated based on stimulus intensity and remifentanil concentration. The surgical stress index (SSI) was developed to correlate with the TSS estimate in the development data set. The performance of SSI was validated within the validation data set during and before surgery, especially at skin incision and during changes of the predicted remifentanil effect-site concentration. RESULTS: SSI was computed as a combination of normalized heart beat interval (HBI(norm)) and plethysmographic pulse wave amplitude (PPGA(norm)): SSI = 100-(0.7*PPGA(norm)+0.3*HBI(norm)). SSI increased at skin incision and stayed higher during surgery than before surgery; SSI responded to remifentanil concentration changes and was higher at the lower concentrations of remifentanil. CONCLUSIONS: SSI reacts to surgical nociceptive stimuli and analgesic drug concentration changes during propofol-remifentanil anaesthesia. Further validation studies of SSI are needed to elucidate its usefulness during other anaesthetic and surgical conditions.

Skin conductance or entropy for detection of non-noxious stimulation during different clinical levels of sedation.

BACKGROUND: State entropy (SE) measures electroencephalographic signals, whereas response entropy (RE) also includes frontal electromyographic activity. In the presence of electromyographic activity, the RE index is larger than the SE index, the difference being denoted as RE-Delta (RE-Delta= RE - SE). Skin conductance (SC) may be expressed by a slow reacting variable, the mean SC level, the derivate of the mean SC level (D-SC), the number of SC fluctuations (NSCF) or the amplitude of the SC fluctuations (ASCF), which directly shows skin sympathetic nerve activity. The goal of this study was to evaluate whether these SC and entropy variables could differentiate between the responses obtained to load sound stimuli at different sedation levels before the induction of general anaesthesia. METHODS: Twenty women scheduled for gynaecological laparotomy were studied. The modified observer's assessment of alertness sedation (OAAS) was used to classify the patients' hypnotic levels. White sounds (98 dB) were given at OAAS level 5 without propofol, at OAAS levels 4-3 and 3-2 with propofol and at OAAS levels 3-2 and < 2 with propofol and remifentanil. RESULTS: RE and SE showed a steady decline from OAAS level 5 to level < 2 (P < 0.01). RE-Delta did not discriminate between any of the OAAS levels (P= NS). The mean SC level discriminated between OAAS levels 4-3 to < 2 (P < 0.01). D-SC discriminated between all the different OAAS levels (P < 0.01). NSCF discriminated between OAAS levels 5 to 3-2 (P < 0.05), but did not discriminate at OAAS level 3-2 between propofol alone or combined with remifentanil, or between OAAS level 3-2 and < 2. ASCF differentiated between OAAS levels 5 and 4 (P < 0.001) and OAAS levels 3-2 and < 2 (P < 0.05) only. CONCLUSION: RE, SE and D-SC showed a similar discrimination between sound responses at the different sedation levels.

Comparison of skin conductance with entropy during intubation, tetanic stimulation and emergence from general anaesthesia.

BACKGROUND: The number of skin conductance fluctuations (NSCF) expresses sympathetic skin nerve activity. The response entropy (RE) measures electromyographic and electroencephalographic activity in the forehead. The state entropy (SE) measures mainly electroencephalographic activity. When the suppression of frontal muscular activity is complete, RE is equal to SE. RE-Delta is defined as SE minus RE. The purposes of this study were to examine whether NSCF and RE-Delta correlate with signs of clinical stress during intubation and tetanic noxious stimulation and to elucidate how rapidly and accurately entropy and NSCF react during emergence from general anaesthesia. METHODS: Twenty women scheduled for gynaecological laparotomy were studied. During intubation in remifentanil and propofol general anaesthesia, NSCF and RE-Delta were correlated with the clinical stress score. After a wash-out period, two series of tetanic stimuli were given, the first with (R+) and the second without (R-) remifentanil infusion. The tetanic pre-stimuli periods were compared with the tetanic post-stimuli periods, and R+ was compared with R-. During emergence, the responses of entropy and skin conductance were related to the time of extubation. RESULTS: NSCF correlated well with the clinical stress score during intubation (r(2)= 0.73, P < 0.0005). RE-Delta showed a weaker correlation (r(2)= 0.33, P= 0.007). During tetanic stimuli, the NSCF pre-stimuli level was lower than the post-stimuli level (P < 0.001), and the NSCF R+ response was lower than the NSCF R- response (P= 0.002). RE-Delta did not show similar differences. During emergence, RE reacted before NSCF and SE (P= 0.003). CONCLUSION: NSCF was better than RE-Delta for the measurement of clinical stress during intubation, and was sensitive to tetanic stimuli at different opioid analgesic levels, by contrast with RE-Delta. Both modalities were able to predict emergence at the end of anaesthesia, but RE was more rapid.

Novel multiparameter approach for measurement of nociception at skin incision during general anaesthesia.

BACKGROUND: Direct indicators for the evaluation of the nociceptive-anti-nociceptive balance during general anaesthesia do not exist. The aim of this study was to combine physiological parameters to obtain such an indicator. METHODS: Fifty-five females scheduled for surgery under general anaesthesia combining target-controlled infusions of propofol and remifentanil were studied. Propofol was given to maintain state entropy (SE) at 50 and remifentanil was targeted at 1, 3 or 5 ng ml(-1). The patients' reactions and clinical signs of nociception, remifentanil levels and estimation of noxious intensity of incision were combined into a clinical score [Clinical Signs-Stimulus-Antinociception (CSSA)] to evaluate the nociceptive-anti-nociceptive balance. ECG, photoplethysmography (PPG), response entropy (RE) and SE were recorded from 60 s before to 120 s after skin incision. Differences between post- and pre-incision values of heart rate variability (HRV), PPG and pulse transition time related parameters were analysed off-line to evidence the best predictors of CSSA. Those best predictors of CSSA served to develop a response index of nociception (RN), scaled from 0 to 100. This index was further tested in 10 additional patients. RESULTS: HRV, RE, RE-SE and PPG variability were the best predictors of CSSA. The prediction probability of RN at predicting CSSA was 0.78. RN response was higher after larger incision, in movers and with lower remifentanil concentrations. CONCLUSIONS: The empirically developed algorithm of RN leads to an index that seems to adequately estimate the nociceptive-anti-nociceptive balance at skin incision during general anaesthesia. In the future, CSSA may serve as a reference for studies investigating methods aimed at evaluating this pharmacodynamic component of anaesthesia.

EEG spectral entropy, heart rate, photoplethysmography and motor responses to skin incision during sevoflurane anaesthesia.

BACKGROUND: Analgesia is a part of balanced anaesthesia, but direct indicators of nociception do not exist. We examined the relationship between motor reactions and physiological variables during skin incision in sevoflurane anaesthesia and hypothesized that nociception could be detected and graded by significant changes in these variables. METHODS: Thirty-one women scheduled for abdominal hysterectomy participated in the study. Anaesthesia was induced with fentanyl (1 microg kg(-1)), propofol (1 mg kg(-1)) and sevoflurane. Skin incision was performed 14 min after induction during 1.6% end-tidal sevoflurane anaesthesia without neuromuscular blockade. Electrocardiography (ECG), photoplethysmography (PPG) and electroencephalography (EEG) were registered, and a range of variables was computed from these signals. The postincision values, normalized with respect to their preincision values, of movers vs. non-movers were compared. The variables showing significant differences between movers and non-movers were used to develop a logistic regression equation for the classification of patients into movers or non-movers. RESULTS: Twenty-six patients were eligible for analysis, and 12 (46%) displayed a motor reaction to skin incision (movers). Many ECG, PPG and EEG-related variables showed significant differences between the pre- and postincision periods. The best classification performance, assessed by leave-one-out cross-validation, between movers and non-movers was achieved with the combination of response entropy of EEG, RR-interval and PPG notch amplitude. The corresponding equation yielded 96% correct classification with 90% sensitivity and 100% specificity. The classification performance of any single variable alone was considerably worse. CONCLUSION: Combination of information from different sources may be required for monitoring the adequacy of analgesia during anaesthesia.