Association of the classification of intraoperative adverse events (ClassIntra) with complications and neurological outcome after neurosurgical procedures: a prospective cohort study.

PURPOSE: To analyze the reliability of the classification of intraoperative adverse events (ClassIntra) to reflect intraoperative complications of neurosurgical procedures and the potential to predict the postoperative outcome including the neurological performance. The ClassIntra classification was recently introduced and found to be reliable for assessing intraoperative adverse events and predicting postoperative complications across different surgical disciplines. Nevertheless, its potential role for neurosurgical procedures remains elusive. METHODS: This is a prospective, monocentric cohort study assessing the ClassIntra in 422 adult patients who underwent a neurosurgical procedure and were hospitalized between July 1, 2021, to December 31, 2021. The primary outcome was the occurrence of intraoperative complications graded according to ClassIntra and the association with postoperative outcome reflected by the Clavien-Dindo classification and comprehensive complication index (CCI). The ClassIntra is defined as intraoperative adverse events as any deviation from the ideal course on a grading scale from grade 0 (no deviation) to grade V (intraoperative death) and was set at sign-out in agreement between neurosurgeon and anesthesiologist. Secondary outcomes were the neurological outcome after surgery as defined by Glasgow Coma Scale (GCS), modified Rankin scale (mRS), Neurologic Assessment in Neuro-Oncology (NANO) scale, National Institute Health of Strokes Scale (NIHSS), and Karnofsky Performance Score (KPS), and need for unscheduled brain scan. RESULTS: Of 442 patients (mean [SD] age, 56.1 [16.2]; 235 [55.7%] women and 187 [44.3%] men) who underwent a neurosurgical procedure, 169 (40.0%) patients had an intraoperative adverse event (iAE) classified as ClassIntra I or higher. The NIHSS score at admission (OR, 1.29; 95% CI, 1.03-1.63, female gender (OR, 0.44; 95% CI, 0.23-0.84), extracranial procedures (OR, 0.17; 95% CI, 0.08-0.61), and emergency cases (OR, 2.84; 95% CI, 1.53-3.78) were independent risk factors for a more severe iAE. A ClassIntra ≥ II was associated with increased odds of postoperative complications classified as Clavien-Dindo (p < 0.01), neurological deterioration at discharge (p < 0.01), prolonged hospital (p < 0.01), and ICU stay (p < 0.01). For elective craniotomies, severity of ClassIntra was associated with the CCI (p < 0.01) and need for unscheduled CT or MRI scan (p < 0.01). The proportion of a ClassIntra ≥ II was significantly higher for emergent craniotomies (56.2%) and associated with in-hospital mortality, and an unfavorable neurological outcome (p < 0.01). CONCLUSION: Findings of this study suggest that the ClassIntra is sensitive for assessing intraoperative adverse events and sufficient to identify patients with a higher risk for developing postoperative complications after a neurosurgical procedure.

Agreement between cardiac output measurements by pulse wave analysis using the Pressure Recording Analytical Method and transthoracic echocardiography in patients with veno-venous extracorporeal membrane oxygenation therapy: An observational method comparison.

BACKGROUND: Measuring cardiac output (CO) is important in patients treated with veno-venous extracorporeal membrane oxygenation (vvECMO) because vvECMO flow and CO need to be balanced. Uncalibrated pulse wave analysis with the Pressure Recording Analytical Method (PRAM) may be suitable to measure CO in patients with vvECMO therapy. OBJECTIVE: To assess the agreement between CO measured by PRAM (PRAM-CO; test method) and CO measured by transthoracic echocardiography (TTE-CO; reference method). DESIGN: A prospective observational method comparison study. SETTING: The ICU of a German university hospital between March and December 2021. PATIENTS: Thirty one adult patients with respiratory failure requiring vvECMO therapy: 29 of the 31 patients (94%) were treated for COVID-19 related respiratory failure. MAIN OUTCOME MEASURES: PRAM-CO and TTE-CO were measured simultaneously at two time points in each patient with at least 20 min between measurements. A radial or femoral arterial catheter-derived blood pressure waveform was used for PRAM-CO measurements. TTE-CO measurements were conducted using the pulsed wave Doppler-derived velocity time integral of the left ventricular outflow tract (LVOT) and the corresponding LVOT diameter. PRAM-CO and TTE-CO were compared using Bland-Altman analysis and the percentage error (PE). We defined a PE of <30% as clinically acceptable. RESULTS: Mean ±â€ŠSD PRAM-CO was 6.86 ±â€Š1.49 l min -1 and mean TTE-CO was 6.94 ±â€Š1.58 l min -1 . The mean of the differences between PRAM-CO and TTE-CO was 0.09 ±â€Š0.73 l min -1 with a lower 95% limit of agreement of -1.34 l min -1 and an upper 95% limit of agreement of 1.51 l min -1 . The PE was 21%. CONCLUSIONS: The agreement between PRAM-CO and TTE-CO is clinically acceptable in adult patients with vvECMO therapy.

Effect of thoracic epidural anesthesia on postoperative outcome in major liver surgery: a retrospective cohort study.

PURPOSE: Postoperative complications after major liver surgery are common. Thoracic epidural anesthesia may provide beneficial effects on postoperative outcome. We strove to compare postoperative outcomes in major liver surgery patients with and without thoracic epidural anesthesia. METHODS: This was a retrospective cohort study in a single university medical center. Patients undergoing elective major liver surgery between April 2012 and December 2016 were eligible for inclusion. We divided patients into two groups according to whether or not they had thoracic epidural anesthesia for major liver surgery. The primary outcome was postoperative hospital length of stay, i.e., from day of surgery until hospital discharge. Secondary outcomes included 30-day postoperative mortality and major postoperative complications. Additionally, we investigated the effect of thoracic epidural anesthesia on perioperative analgesia doses and the safety of thoracic epidural anesthesia. RESULTS: Of 328 patients included in this study, 177 (54.3%) received thoracic epidural anesthesia. There were no clinically important differences in postoperative hospital length of stay (11.0 [7.00-17.0] vs. 9.00 [7.00-14.0] days, p = 0.316, primary outcome), death (0.0 vs. 2.7%, p = 0.995), or the incidence of postoperative renal failure (0.6 vs. 0.0%, p = 0.99), sepsis (0.0 vs. 1.3%, p = 0.21), or pulmonary embolism (0.6 vs. 1.4%, p = 0.59) between patients with or without thoracic epidural anesthesia. Perioperative analgesia doses - including the intraoperative sufentanil dose (0.228 [0.170-0.332] vs. 0.405 [0.315-0.565] µg·kg-1·h-1, p < 0.0001) - were lower in patients with thoracic epidural anesthesia. No major thoracic epidural anesthesia-associated infections or bleedings occurred. CONCLUSION: This retrospective analysis suggests that thoracic epidural anesthesia does not reduce postoperative hospital length of stay in patients undergoing major liver surgery - but it may reduce perioperative analgesia doses. Thoracic epidural anesthesia was safe in this cohort of patients undergoing major liver surgery. These findings need to be confirmed in robust clinical trials.

Validation of three nociception indices to predict immediate postoperative pain before emergence from general anaesthesia: a prospective double-blind, observational study.

BACKGROUND: Nociception monitoring devices are designed to estimate nociception during general anaesthesia. We evaluated the predictive accuracy of heart rate and three nociception indices to predict postoperative pain before emergence from general anaesthesia. METHODS: In patients undergoing trauma or orthopaedic surgery, HR, Surgical Pleth Index® (SPI), Pupillary Pain Index® (PPI), and Nociception Level® (NOL) were simultaneously recorded for 5 min after the end of surgery but before return of consciousness. After admission to the recovery room, pain scores were assessed regularly for 2 h. HR, SPI, PPI, and NOL were analysed for their predictive accuracy of postoperative pain and opioid consumption with assessment of area under the receiver operating characteristic (AUC) curves, Spearman rank-correlation coefficient, and regression modelling. RESULTS: Data for 60 subjects were analysed. The AUC (95% confidence interval [95% CI]) of the predictive accuracy for moderate-to-severe postoperative pain differed between nociception indices (HR=0.46 [0.29-0.64], P=0.671; SPI=0.46 [0.31-0.61], P=0.621; PPI=0.52 [0.36-0.68], P=0.770; NOL=0.66 [0.51-0.81], P=0.038). In a multivariable logistic regression model, a higher predictive accuracy was found for a multivariable predictor combining NOL values with ASA physical status and information about use of regional anaesthesia (AUC=0.83 [0.72-0.94], P<0.001). CONCLUSIONS: Heart rate, Surgical Pleth Index, Pupillary Pain Index, and Nociception Level measured before emergence from general anaesthesia do not yet have sufficient diagnostic accuracy for prediction of postoperative pain. CLINICAL TRIAL REGISTRATION: NCT05063227.

The impact of spinal anaesthesia on perioperative opioid consumption, postoperative pain and oncological outcome in radical retropubic prostatectomy-a retrospective before-and-after effectiveness study.

BACKGROUND: Spinal anaesthesia preceding general anaesthesia has been conducted for open radical retropubic prostatectomy (RRP) to decrease immediate postoperative pain for many years. Nevertheless, the effectiveness of spinal anaesthesia to reduce postoperative opioid requirements remains unknown. The aim of the present study was to determine the effect of spinal anaesthesia preceding general anaesthesia on opioid requirements, postoperative pain and biochemical cancer-free survival. METHODS: This before-and-after effectiveness study investigated effects of two different anaesthesia techniques in 636 patients with RRP. Three hundred eighteen consecutive patients in the SPA group (spinal anaesthesia preceding general anaesthesia) were compared with 318 patients in the GA group (general anaesthesia alone). The primary endpoint of the study was opioid consumption in the post-anaesthesia care unit. Secondary endpoints were intraoperative opioid consumption, postoperative pain, postoperative recovery time, the length of hospital-stay, persistence of pain 1 year after surgery and cancer-free survival. Differences between the groups were analysed by a two-sided t-test, χ2-test, Fisher's exact test and Mann-Whitney U test and the influence of possible confounders on opioid consumption with a general linear model. Cancer-free survival was determined by Kaplan-Meier curves and group differences by log-rank tests and multivariable Cox regression analyses. RESULTS: The total amount of morphine equivalent administered postoperatively was 7.5 [6.9; 8.1] mg in the SPA group and 6.0 [5.5; 6.5] mg in the GA group (mean [95% CI], p < 0.001). The amount of intraoperative sufentanil was 56.9 [55.1; 58.7] µg in the SPA group and 84.5 [82.5; 86.5] µg in the GA group (mean [95% CI], p < 0.001). There was no difference found in the postoperative pain level, length of hospital-stay and pain level 1 year after surgery. Biochemical cancer-free survival was highly related to TNM stage (p < 0.001, pT3 vs. pT2 hazard ratio 5.4 [95%CI 3.3; 9.2]) but not to the type of anaesthesia (p = 0.29). CONCLUSIONS: Spinal anaesthesia preceding general anaesthesia for RRP is associated with increased postoperative opioid consumption compared to general anaesthesia alone. Postoperative pain level and the oncological outcome are not affected by the adjunctive use of spinal anaesthesia. Thus, the addition of spinal anaesthesia to general anaesthesia has no advantage in RRP. TRIAL REGISTRATION: ClinicalTrial.gov, NCT03565705.

A new noninvasive finger sensor (NICCI system) for continuous blood pressure and pulse pressure variation monitoring: A method comparison study in patients having neurosurgery.

BACKGROUND: The NICCI system (Getinge, Gothenburg, Sweden) is a new noninvasive haemodynamic monitoring system using a finger sensor. OBJECTIVES: We aimed to investigate the performance of the NICCI system to measure blood pressure and pulse pressure variation compared with intra-arterial measurements. DESIGN: A prospective method comparison study. SETTING: University Medical Center Hamburg-Eppendorf, Hamburg, Germany. PATIENTS: Forty-seven neurosurgery patients. MAIN OUTCOME MEASURES: We performed a method comparison study in 47 neurosurgery patients to compare NICCI blood pressure measurements (BP NICCI ) with intra-arterial blood pressure measurements (BP ART ) (Bland-Altman analysis, four-quadrant plot, error grid analysis) and NICCI pulse pressure variation measurements (PPV NICCI ) with pulse pressure variation calculated manually from the intra-arterial blood pressure waveform (PPV ART ) (Bland-Altman analysis, predictive agreement, Cohen's kappa). RESULTS: The mean of the differences ±â€Šstandard deviation (95% limits of agreement) between BP NICCI and BP ART was 11 ±â€Š10 mmHg (-8 to 30 mmHg) for mean blood pressure (MBP), 3 ±â€Š12 mmHg (-21 to 26 mmHg) for systolic blood pressure (SBP) and 12 ±â€Š10 mmHg (-8 to 31 mmHg) for diastolic blood pressure (DBP). In error grid analysis, 54% of BP NICCI and BP ART MBP measurement pairs were classified as 'no risk', 43% as 'low risk', 3% as 'moderate risk' and 0% as 'significant risk' or 'dangerous risk'. The mean of the differences between PPV NICCI and PPV ART was 1 ±â€Š3% (-4 to 6%). The predictive agreement between PPV NICCI and PPV ART was 80% and Cohen's kappa was 0.55. CONCLUSIONS: The absolute agreement between BP NICCI and BP ART was not clinically acceptable. We recommend not using the current version of the NICCI system for blood pressure monitoring during surgery. The absolute agreement between PPV NICCI and PPV ART was clinically acceptable with moderate predictive agreement regarding pulse pressure variation categories. The NICCI system needs to be further developed and re-evaluated when an improved version is available. TRIAL REGISTRATION: The study was registered in the German Clinical Trials Register (DRKS00023188) on 2 October 2020.

Continuous intra-arterial versus intermittent oscillometric arterial pressure monitoring and hypotension during induction of anaesthesia: the AWAKE randomised trial.

BACKGROUND: Hypotension during induction of anaesthesia is associated with organ injury. Continuous arterial pressure monitoring might help reduce hypotension. We tested the hypothesis that continuous intra-arterial compared with intermittent oscillometric arterial pressure monitoring reduces hypotension during induction of anaesthesia in noncardiac surgery patients. METHODS: In this single-centre randomised trial, 242 noncardiac surgery patients in whom intra-arterial arterial pressure monitoring was planned were randomised to unblinded continuous intra-arterial or to intermittent oscillometric arterial pressure monitoring (with blinded intra-arterial arterial pressure monitoring) during induction of anaesthesia. The primary endpoint was the area under a mean arterial pressure (MAP) of 65 mm Hg within the first 15 min of induction of anaesthesia. Secondary endpoints included areas under MAP values of 60, 50, and 40 mm Hg and durations of MAP values <65, <60, <50, and <40 mm Hg. RESULTS: There were 224 subjects available for analysis. The median (25th-75th percentile) area under a MAP of 65 mm Hg was 15 (2-36) mm Hg • min in subjects assigned to continuous intra-arterial monitoring and 46 (7-111) mm Hg • min in subjects assigned to intermittent oscillometric monitoring (P<0.001). Subjects assigned to continuous intra-arterial monitoring had smaller areas under MAP values of 60, 50, and 40 mm Hg and shorter durations of MAP values <65, <60, <50, and <40 mm Hg than subjects assigned to intermittent oscillometric monitoring. CONCLUSION: Continuous intra-arterial arterial pressure monitoring reduces hypotension during induction of anaesthesia compared with intermittent oscillometric arterial pressure monitoring in noncardiac surgery patients. In patients for whom an arterial catheter is planned, clinicians might therefore consider inserting the arterial catheter before rather than after induction of anaesthesia. CLINICAL TRIALS REGISTRATION: NCT04894019.

Effect of sedative premedication with oral midazolam on postanesthesia care unit delirium in older adults: a secondary analysis following an uncontrolled before-after design.

BACKGROUND: Sedative premedication with benzodiazepines has been linked with prolonged recovery and inadequate emergence during the immediate postoperative period. We aimed to analyze the association between postanesthesia care unit (PACU) delirium and sedative premedication with oral midazolam. METHODS: We performed a secondary analysis of prospectively collected data before (midazolam cohort) and after (non-midazolam cohort) implementation of a restrictive strategy for oral premedication with midazolam. From March 2015 until July 2018, we included patients 60 years and older, who underwent elective radical prostatectomy for prostate cancer. Exclusion criteria were contraindications to premedication with midazolam, preoperative anxiety, and a history of neurological disorders. Patients, who were scheduled for postoperative admission to the intensive care unit, were excluded. Between 2015 and 2016, patients received 7.5 mg oral midazolam preoperatively (midazolam cohort). Patients included between 2017 and 2018 did not receive any sedative medication preoperatively (non-midazolam cohort). The primary endpoint was the incidence of PACU delirium. RESULTS: PACU delirium rates were 49% in the midazolam cohort (n = 214) and 33% in the non-midazolam cohort (n = 218). This difference was not statistically significant on multivariable logistic regression analysis (OR 0.847 [95% CI 0.164; 4.367]; P = 0.842). Age (OR 1.102 [95% CI 1.050; 1.156]; P < 0.001), the cumulative dose of sufentanil (OR 1.014 [95% CI 1.005; 1.024]; P = 0.005), and propofol-sufentanil for anesthesia maintenance (OR 2.805 [95% CI 1.497; 5.256]; P = 0.001) were significantly associated with PACU delirium. CONCLUSION: Midazolam for sedative premedication was not significantly associated with PACU delirium. The reduction in the incidence of PACU delirium throughout the study period may be attributable to improvements in perioperative management other than a more restrictive preoperative benzodiazepine administration.

Impact of postanesthesia care unit delirium on self-reported cognitive function and perceived health status: a prospective observational cohort study.

PURPOSE: The objective of this study was to determine the influence of postanesthesia care unit (PACU) delirium on self-reported cognitive function and perceived health status 3 months after surgery. METHODS: This prospective observational cohort study was performed in a PACU at a high-volume prostate cancer center. We used a convenience sample of patients > 60 years undergoing elective radical prostatectomy. Patients with a history of cerebrovascular or neurodegenerative disease were excluded. Fifteen, 30, 45, and 60 following extubation, patients were screened for signs of delirium with the Confusion Assessment Method for the Intensive Care Unit. Three months after surgery self-reported cognitive function was assessed with the Cognitive Failures Questionnaire, and health status was evaluated with the 36-item Short-Form Health Survey (SF-36). RESULTS: Signs of PACU delirium were present in 32.4% (n = 72/222) of patients, and 80.2% (n = 178/222) completed the 3-month follow-up. The presence of PACU delirium signs was not significantly associated with self-reported cognitive failures (B = 0.60, 95% CI: -1.72; 2.92, p = 0.61) or SF-36 physical component scores (B = 0.19, 95% CI: 0.02; 0.36, p = 0.03) or SF-36 mental component scores (B = -0.03, 95% CI: -0.18, 0.11, p = 0.66) 3 months after radical prostatectomy. CONCLUSIONS: In a cohort of educated, highly functioning, elderly male patients who were assessed immediately after surgery and at a 3-month follow-up, we found no association between PACU delirium and self-reported cognitive failures or perceived health status, which implies that PACU delirium may be an event of limited duration and impact. TRIAL REGISTRATION: The study was registered at ClinicalTrials.gov (Identifier: NCT04168268, Date of registration: November 19, 2019).

[Nociception monitoring : Method for intraoperative opioid control?] / Nozizeptionsmonitoring : Methode zur intraoperativen Opioidsteuerung?

The intraoperative dosing of opioids is a challenge in routine anesthesia as the potential effects of intraoperative overdosing and underdosing are not completely understood. In recent years an increasing number of monitors were approved, which were developed for the detection of intraoperative nociception and therefore should enable a better control of opioid titration. The nociception monitoring devices use either continuous hemodynamic, galvanic or thermal biosignals reflecting the balance between parasympathetic and sympathetic activity, measure the pupil dilatation reflex or the nociceptive flexor reflex as a reflexive response to application of standardized nociceptive stimulation. This review article presents the currently available nociception monitors. Most of these monitoring devices detect nociceptive stimulations with higher sensitivity and specificity than changes in heart rate, blood pressure or sedation depth monitoring devices. There are only few studies on the effect of opioid titration guided by nociception monitoring and the possible postoperative benefits of these devices. All nociception monitoring techniques are subject to specific limitations either due to perioperative confounders (e.g. hypovolemia) or special accompanying medical conditions (e.g. muscle relaxation). There is an ongoing discussion about the clinical relevance of nociceptive stimulation in general anesthesia and the effect on patient outcome. Initial results for individual monitor systems show a reduction in opioid consumption and in postoperative pain level. Nevertheless, current evidence does not enable the routine use of nociception monitoring devices to be recommended as a clear beneficial effect on long-term outcome has not yet been proven.

Relationship Between Intraoperative and Preoperative Ambulatory Nighttime Heart Rates: A Secondary Analysis of a Prospective Observational Study.

BACKGROUND: It remains unknown what constitutes physiologically relevant intraoperative bradycardia. Intraoperative bradycardia is usually defined using absolute heart rate thresholds, ignoring preoperative baseline heart rates. In contrast, we considered defining intraoperative bradycardia relative to preoperative ambulatory nighttime heart rate. Specifically, we hypothesized that the individual mean intraoperative heart rate is lower than the mean preoperative ambulatory nighttime heart rate. We, therefore, sought to investigate the relationship between the intraoperative and preoperative ambulatory nighttime heart rates in adults having noncardiac surgery with general anesthesia. Additionally, we sought to investigate the incidence of intraoperative bradycardia using relative versus absolute heart rate thresholds. METHODS: We conducted a secondary analysis of a database from a prospective study including preoperative ambulatory and intraoperative heart rates in 363 patients having noncardiac surgery with general anesthesia. RESULTS: The mean intraoperative heart rate was lower than the mean nighttime heart rate (mean difference, -9 bpm; 95% confidence interval [CI], -10 to -8 bpm; P < .001). The mean intraoperative heart rate was lower than the mean nighttime heart rate in 319 of 363 patients (88%; 95% CI, 84%-91%). The incidence of intraoperative bradycardia was 42% (95% CI, 38%-47%) when it was defined as intraoperative heart rate >30% lower than mean nighttime heart rate and 43% (95% CI, 38%-49%) when it was defined as intraoperative heart rate <45 bpm. CONCLUSIONS: The mean intraoperative heart rate is lower than the mean nighttime heart rate in about 9 of 10 patients. Intraoperative bradycardia might thus be physiologically and clinically important. Future research needs to investigate whether there is an association between intraoperative bradycardia and postoperative outcomes.

Nociception level-guided opioid administration in radical retropubic prostatectomy: a randomised controlled trial.

BACKGROUND: This RCT investigated the effect of opioid titration by three different nociception monitoring devices or clinical signs during general anaesthesia. METHODS: Ninety-six patients undergoing radical retropubic prostatectomy with propofol/remifentanil anaesthesia were randomised into one of four groups to receive remifentanil guided by one of three nociception monitoring devices (surgical pleth index [SPI], pupillary pain index [PPI], or nociception level [NOL]) or by clinical judgement (control). Intraoperative remifentanil requirement was the primary endpoint, whereas recovery parameters and stress hormone levels were secondary endpoints. RESULTS: The mean [95% confidence interval {CI}] remifentanil administration rate differed between the groups: control 0.34 (0.32-0.37), SPI 0.46 (0.38-0.55), PPI 0.07 (0.06-0.08), and NOL 0.16 (0.12-0.21) µg kg-1 min-1(P<0.001). Intraoperative cessation of remifentanil administration occurred in different numbers (%) of patients: control 0 (0%), SPI 1 (4.3%), PPI 18 (75.0%), and NOL 11 (47.8%); P=0.002. The area under the curve analyses indicated differences in cumulative cortisol levels (mg L-1 min-1) amongst the groups: control 37.9 (33.3-43.1), SPI 38.6 (33.8-44.2), PPI 72.1 (63.1-82.3), and NOL 54.4 (47.6-62.1) (mean [95% CI]). Pairwise group comparison results were as follows: control vs SPI, P=0.830; control vs PPI, P<0.001; control vs NOL, P=0.001; SPI vs PPI, P<0.001; SPI vs NOL, P=0.002; and PPI vs NOL, P=0.009. CONCLUSIONS: The nociception monitoring devices and clinical signs reflect the extent of nociception differently, leading to dissimilar doses of remifentanil. Very low remifentanil doses were associated with an increase and higher remifentanil doses were accompanied by a decrease in serum cortisol concentrations. Use of nociception monitoring devices for guiding intra-operative opioid dosing needs further validation. CLINICAL TRIAL REGISTRATION: NCT03380949.

Guiding Opioid Administration by 3 Different Analgesia Nociception Monitoring Indices During General Anesthesia Alters Intraoperative Sufentanil Consumption and Stress Hormone Release: A Randomized Controlled Pilot Study.

BACKGROUND: This pilot study investigated the effect of sufentanil titration by 3 different analgesia monitoring devices or clinical signs during general anesthesia. METHODS: Forty-eight patients undergoing radical retropubic prostatectomy with sevoflurane/sufentanil anesthesia were randomly assigned into 4 groups and received sufentanil guided either by 1 of 3 analgesia monitoring devices (Surgical Pleth Index [SPI], Pupillary Pain Index [PPI], Nociception Level [NoL]) or by clinical judgment (control). The primary end point was intraoperative sufentanil consumption. Adrenocorticotropic hormone (ACTH) and cortisol were measured at 4 time points during the day of surgery. Data were analyzed by Kruskal-Wallis and Mann-Whitney U tests and by mixed model and area under the curve (AUC) analyses for group comparisons and time effects of stress hormones. RESULTS: The total amount of sufentanil administration (µg·kg·minute·10) differed between the groups (median [quartiles]: control = 5.6 [4.4-6.4], SPI = 7.2 [4.8-8.4], PPI = 2.0 [1.8-2.9], NoL = 3.8 [3.3-5.1]; PPI versus SPI, -5.1 [-6.6 to -1.3], P < .001; NoL versus SPI, -3.0 [-5.2 to 0.2], P = .024; control versus SPI, -1.6 [-3.7 to 1.7], P = .128; NoL versus PPI, 1.7 [0.6-3.4], P < .001; control versus PPI, 3.4 [2.0-4.6], P < .001; control versus NoL, 1.6 [-0.2 to 3.3], P = .017) (Hodges-Lehmann estimator [99% confidence interval {CI}], P values). The AUC analysis indicated differences among groups in cumulative ACTH levels (ng·liter·minute, natural logarithm (ln)-transformed data) of NoL versus PPI (-1.079 [-1.950 to -0.208], P = .001) and PPI versus SPI (1.192 [0.317-2.068], P= .001), as well as differences in cortisol levels (µg·liter·minute) for PPI versus SPI (46,710 [21,145-72,274], P < .001), NoL versus SPI (27,645 [3163-52,126], P = .003), and control versus SPI (31,824 [6974-56,675], P = .001) (differences in means [99% CI], P value). Secondary end points (postoperative recovery, pain level, and analgesia medication) showed no differences. CONCLUSIONS: The type of analgesia nociception monitoring affected the total amount of sufentanil administered. Lower sufentanil doses in the PPI group were associated with an increased endocrine stress response. Titration by SPI caused no opioid reduction compared to the control but was associated with a reduced endocrine stress response.

Validation of Innovative Techniques for Monitoring Nociception during General Anesthesia: A Clinical Study Using Tetanic and Intracutaneous Electrical Stimulation.

BACKGROUND: This study compares the analgesic indices Analgesia Nociception Index (heart rate variability), Surgical Pleth Index (photoplethysmography), and pupillary dilatation, to heart rate, mean arterial pressure, and bispectral index, with regard to diagnostic accuracy and prediction probability for nociceptive response. The primary endpoint was the correlation between Δ values and the remifentanil dose administered. METHODS: We anesthetized 38 patients with propofol and increasing doses of remifentanil and applied standardized tetanic and intracutaneous electrical painful stimulations on each analgesic level. Baseline and Δ values of the Analgesia Nociception Index, the Surgical Pleth Index, pupillary dilatation, heart rate, mean arterial pressure, and bispectral index and their relation to remifentanil doses were analyzed by receiver operating characteristic curves, prediction probability (PK), and mixed-model analysis. RESULTS: Under propofol sedation, sensitivity and specificity of the Analgesia Nociception Index (PK = 0.98), the Surgical Pleth Index (PK = 0.87), and pupillary dilatation (PK = 0.98) for detecting both painful stimulations were high compared to heart rate (PK = 0.74), mean arterial pressure (PK = 0.75), and bispectral index (PK = 0.55). Baseline values had limited prediction probability toward the nociceptive response (Analgesia Nociception Index: PK = 0.7; Surgical Pleth Index: PK = 0.63; pupillary dilatation: PK = 0.67; and bispectral index: PK = 0.67). The remifentanil dose had an effect (P < 0.001) on all parameters except for bispectral index (P = 0.216). CONCLUSIONS: The Analgesia Nociception Index, the Surgical Pleth Index, and pupillary dilatation are superior in detecting painful stimulations compared to heart rate and mean arterial pressure but had limited predictive value. These effects are attenuated by increasing dosages of remifentanil. Our data confirm that bispectral index is not a marker of analgesia.

Effect of an interactive cardiopulmonary resuscitation assist device with an automated external defibrillator synchronised with a ventilator on the CPR performance of emergency medical service staff: a randomised simulation study.

BACKGROUND: The present study evaluates whether the quality of advanced cardiac life support (ALS) is improved with an interactive prototype assist device. This device consists of an automated external defibrillator linked to a ventilator and provides synchronised visual and acoustic instructions for guidance through the ALS algorithm and assistance for face-mask ventilations. METHODS: We compared the cardiopulmonary resuscitation (CPR) quality of emergency medical system (EMS) staff members using the study device or standard equipment in a mannequin simulation study with a prospective, controlled, randomised cross-over study design. Main outcome was the effect of the study device compared to the standard equipment and the effect of the number of prior ALS trainings of the EMS staff on the CPR quality. Data were analysed using analyses of covariance (ANCOVA) and binary logistic regression, accounting for the study design. RESULTS: In 106 simulations of 56 two-person rescuer teams, the mean hands-off time was 24.5% with study equipment and 23.5% with standard equipment (Difference 1.0% (95% CI: -0.4 to 2.5%); p = 0.156). With both types of equipment, the hands-off time decreased with an increasing cumulative number of previous CPR trainings (p = 0.042). The study equipment reduced the mean time until administration of adrenaline (epinephrine) by 23 s (p = 0.003) and that of amiodarone by 17 s (p = 0.016). It also increased the mean number of changes in the person doing chest compressions (0.6 per simulation; p < 0.001) and decreased the mean number of chest compressions (2.8 per minute; p = 0.022) and the mean number of ventilations (1.8 per minute; p < 0.001). The chance of administering amiodarone at the appropriate time was higher, with an odds ratio of 4.15, with the use of the study equipment CPR.com compared to the standard equipment (p = 0.004). With an increasing number of prior CPR trainings, the time intervals in the ALS algorithm until the defibrillations decreased with standard equipment but increased with the study device. CONCLUSIONS: EMS staff with limited training in CPR profit from guidance through the ALS algorithm by the study device. However, the study device somehow reduced the ALS quality of well-trained rescuers and thus can only be recommended for ALS provider with limited experience.

Relationship between Sevoflurane Plasma Concentration, Clinical Variables and Bispectral Index Values during Cardiopulmonary Bypass.

BACKGROUND: Anesthetic administration is increasingly guided by electroencephalography (EEG)-based monitoring, such as the bispectral index (BIS). However, during cardiopulmonary bypass (CPB), factors other than the administered hypnotic agents may influence EEG signals, and their effects on BIS values are unknown. METHODS: This report is a secondary analysis of data from a prospective, controlled interventional study comparing the effect of sevoflurane administration guided by BIS monitoring (group SevoBIS) and constant administration of sevoflurane (group Sevo1.8Vol%) during CPB. Sevoflurane plasma concentration (SPC) was measured using gas chromatography. The relationships of BIS to SPC, CPB pump flow, arterial pressure, hematocrit, temperature, time on CPB, and patient characteristics were analysed. RESULTS: No association was observed between BIS values and SPC in group SevoBIS. In group Sevo1.8Vol%, a 40 µg ml-1 increase in SPC, which encompassed the entire range of observed values of the SPC in this analysis, was associated with a decrease of 3.6 (95% confidence interval (CI): 1.1-6.1) in BIS values (p = 0.005). Each increase in CPB time of 10 minutes was associated with an increase in BIS values of 0.25 (95%CI: 0.11-0.39, p<0.001). Path analysis revealed that the BIS values of SevoBIS patients were 5.3 (95%CI: 3.2-7.5) units higher than those of Sevo1.8Vol% patients (p<0.001), which was the strongest effect on BIS values. Path analysis revealed a slope of 0.5 (95%CI: 0.3-0.7) BIS units per 1°C body temperature (p<0.001). CONCLUSION: BIS monitoring is insensitive to clinically relevant changes in SPC in individual patients during CPB.

Providers with Limited Experience Perform Better in Advanced Life Support with Assistance Using an Interactive Device with an Automated External Defibrillator Linked to a Ventilator.

BACKGROUND: Medical teams with limited experience in performing advanced life support (ALS) or with a low frequency of cardiopulmonary resuscitation (CPR) while on duty, often have difficulty complying with CPR guidelines. OBJECTIVE: This study evaluated whether the quality of CPR of trained medical students, who served as an example of teams with limited experience in ALS, could be improved with device assistance. The primary outcome was the hands-off time (i.e., the percentage of the entire CPR time without chest compressions). The secondary outcome was seven time intervals, which should be as short as possible, and the quality of ventilations and chest compressions on the mannequin. METHODS: We compared standard CPR equipment to an interactive device with visual and acoustic instructions for ALS workflow measures to guide briefly trained medical students through the ALS algorithm in a full-scale mannequin simulation study with a randomized crossover study design. The study equipment consisted of an automatic external defibrillator and ventilator that were electronically linked and communicating as a single system. Included were regular medical students in the third to sixth years of medical school of one class who provided written informed consent for voluntary participation and for the analysis of their CPR performance data. No exclusion criteria were applied. For statistical measures of evaluation we used an analysis of variance for crossover trials accounting for treatment effect, sequence effect, and carry-over effect, with adjustment for prior practical experience of the participants. RESULTS: Forty-two medical students participated in 21 CPR sessions, each using the standard and study equipment. Regarding the primary end point, the study equipment reduced the hands-off time from 40.1% (95% confidence interval [CI] 36.9-43.4%) to 35.6% (95% CI 32.4-38.9%, p = 0.031) compared with the standard equipment. Within the prespecified secondary end points, study equipment reduced the time interval until the first rescuer changeover from 273 s (95% CI 244-302 s) to 223 s (95% CI 194-253 s, p = 0.001) and increased the percentage of ventilations with a correct tidal volume of 400-600 mL from 34.3% (95% CI 19.0-49.6%) to 60.9% (95% CI 45.6-76.2%, p = 0.018). CONCLUSIONS: The assist device increased the rescuers' CPR quality. CPR providers with limited experience or a limited frequency of CPR performance (i.e., rural Emergency Medical Services crew) may potentially benefit from this assist device.