Matthias Haenggi

Multicentre study on peri- and postoperative central venous oxygen saturation in high-risk surgical patients

IntroductionLow central venous oxygen saturation (ScvO2) has been associated with increased risk of postoperative complications in high-risk surgery. Whether this association is centre-specific or more generalisable is not known. The aim of this study was to assess the association between peri- and postoperative ScvO2 and outcome in high-risk surgical patients in a multicentre setting.MethodsThree large European university hospitals (two in Finland, one in Switzerland) participated. In 60 patients with intra-abdominal surgery lasting more than 90 minutes, the presence of at least two of Shoemakers criteria, and ASA (American Society of Anesthesiologists) class greater than 2, ScvO2 was determined preoperatively and at two hour intervals during the operation until 12 hours postoperatively. Hospital length of stay (LOS) mortality, and predefined postoperative complications were recorded.ResultsThe age of the patients was 72 ± 10 years (mean ± standard deviation), and simplified acute physiology score (SAPS II) was 32 ± 12. Hospital LOS was 10.5 (8 to 14) days, and 28-day hospital mortality was 10.0%. Preoperative ScvO2 decreased from 77% ± 10% to 70% ± 11% (p < 0.001) immediately after surgery and remained unchanged 12 hours later. A total of 67 postoperative complications were recorded in 32 patients. After multivariate analysis, mean ScvO2 value (odds ratio [OR] 1.23 [95% confidence interval (CI) 1.01 to 1.50], p = 0.037), hospital LOS (OR 0.75 [95% CI 0.59 to 0.94], p = 0.012), and SAPS II (OR 0.90 [95% CI 0.82 to 0.99], p = 0.029) were independently associated with postoperative complications. The optimal value of mean ScvO2 to discriminate between patients who did or did not develop complications was 73% (sensitivity 72%, specificity 61%).ConclusionLow ScvO2 perioperatively is related to increased risk of postoperative complications in high-risk surgery. This warrants trials with goal-directed therapy using ScvO2 as a target in high-risk surgery patients.Introduction Low central venous oxygen saturation (ScvO2) has been associated with increased risk of postoperative complications in high-risk surgery. Whether this association is centre-specific or more generalisable is not known. The aim of this study was to assess the association between peri- and postoperative ScvO2 and outcome in high-risk surgical patients in a multicentre setting. Methods Three large European university hospitals (two in Finland, one in Switzerland) participated. In 60 patients with intra-abdominal surgery lasting more than 90 minutes, the presence of at least two of Shoemakers criteria, and ASA (American Society of Anesthesiologists) class greater than 2, ScvO2 was determined preoperatively and at two hour intervals during the operation until 12 hours postoperatively. Hospital length of stay (LOS) mortality, and predefined postoperative complications were recorded. Results The age of the patients was 72 ± 10 years (mean ± standard deviation), and simplified acute physiology score (SAPS II) was 32 ± 12. Hospital LOS was 10.5 (8 to 14) days, and 28-day hospital mortality was 10.0%. Preoperative ScvO2 decreased from 77% ± 10% to 70% ± 11% (p < 0.001) immediately after surgery and remained unchanged 12 hours later. A total of 67 postoperative complications were recorded in 32 patients. After multivariate analysis, mean ScvO2 value (odds ratio [OR] 1.23 [95% confidence interval (CI) 1.01 to 1.50], p = 0.037), hospital LOS (OR 0.75 [95% CI 0.59 to 0.94], p = 0.012), and SAPS II (OR 0.90 [95% CI 0.82 to 0.99], p = 0.029) were independently associated with postoperative complications. The optimal value of mean ScvO2 to discriminate between patients who did or did not develop complications was 73% (sensitivity 72%, specificity 61%). Conclusion Low ScvO2 perioperatively is related to increased risk of postoperative complications in high-risk surgery. This warrants trials with goal-directed therapy using ScvO2 as a target in high-risk surgery patients.

Intra- and inter-individual variation of BIS-index® and Entropy® during controlled sedation with midazolam/remifentanil and dexmedetomidine/remifentanil in healthy volunteers: an interventional study

IntroductionWe studied intra-individual and inter-individual variability of two online sedation monitors, BIS® and Entropy®, in volunteers under sedation.MethodsTen healthy volunteers were sedated in a stepwise manner with doses of either midazolam and remifentanil or dexmedetomidine and remifentanil. One week later the procedure was repeated with the remaining drug combination. The doses were adjusted to achieve three different sedation levels (Ramsay Scores 2, 3 and 4) and controlled by a computer-driven drug-delivery system to maintain stable plasma concentrations of the drugs. At each level of sedation, BIS® and Entropy® (response entropy and state entropy) values were recorded for 20 minutes. Baseline recordings were obtained before the sedative medications were administered.ResultsBoth inter-individual and intra-individual variability increased as the sedation level deepened. Entropy® values showed greater variability than BIS® values, and the variability was greater during dexmedetomidine/remifentanil sedation than during midazolam/remifentanil sedation.ConclusionsThe large intra-individual and inter-individual variability of BIS® and Entropy® values in sedated volunteers makes the determination of sedation levels by processed electroencephalogram (EEG) variables impossible. Reports in the literature which draw conclusions based on processed EEG variables obtained from sedated intensive care unit (ICU) patients may be inaccurate due to this variability.Trial registrationclinicaltrials.gov Nr. NCT00641563.

Entropy and bispectral index for assessment of sedation, analgesia and the effects of unpleasant stimuli in critically ill patients: an observational study.

IntroductionSedative and analgesic drugs are frequently used in critically ill patients. Their overuse may prolong mechanical ventilation and length of stay in the intensive care unit. Guidelines recommend use of sedation protocols that include sedation scores and trials of sedation cessation to minimize drug use. We evaluated processed electroencephalography (response and state entropy and bispectral index) as an adjunct to monitoring effects of commonly used sedative and analgesic drugs and intratracheal suctioning.MethodsElectrodes for monitoring bispectral index and entropy were placed on the foreheads of 44 critically ill patients requiring mechanical ventilation and who previously had no brain dysfunction. Sedation was targeted individually using the Ramsay Sedation Scale, recorded every 2 hours or more frequently. Use of and indications for sedative and analgesic drugs and intratracheal suctioning were recorded manually and using a camera. At the end of the study, processed electroencephalographical and haemodynamic variables collected before and after each drug application and tracheal suctioning were analyzed. Ramsay score was used for comparison with processed electroencephalography when assessed within 15 minutes of an intervention.ResultsThe indications for boli of sedative drugs exhibited statistically significant, albeit clinically irrelevant, differences in terms of their association with processed electroencephalographical parameters. Electroencephalographical variables decreased significantly after bolus, but a specific pattern in electroencephalographical variables before drug administration was not identified. The same was true for opiate administration. At both 30 minutes and 2 minutes before intratracheal suctioning, there was no difference in electroencephalographical or clinical signs in patients who had or had not received drugs 10 minutes before suctioning. Among patients who received drugs, electroencephalographical parameters returned to baseline more rapidly. In those cases in which Ramsay score was assessed before the event, processed electroencephalography exhibited high variation.ConclusionsUnpleasant or painful stimuli and sedative and analgesic drugs are associated with significant changes in processed electroencephalographical parameters. However, clinical indications for drug administration were not reflected by these electroencephalographical parameters, and barely by sedation level before drug administration or tracheal suction. This precludes incorporation of entropy and bispectral index as target variables for sedation and analgesia protocols in critically ill patients.

Measuring depth of sedation with auditory evoked potentials during controlled infusion of propofol and remifentanil in healthy volunteers.

Avoiding excessively deep levels of sedation is a major problem in intensive care patients. We studied whether clinically relevant levels of sedation can be objectively assessed using long latency auditory evoked potentials. We measured the auditory evoked potentials at 100 ms after the stimulus (N100) in 10 healthy volunteers during stepwise increasing, clinically relevant levels of sedation (Ramsay score [RS] 2–4). The volunteers were studied on three separate occasions and received an infusion of either propofol or a combination of propofol and remifentanil. Effects of remifentanil infusion alone were tested during target controlled infusion (target plasma concentrations: 1, 2, and 3 ng/mL). Remifentanil did not affect evoked potential amplitudes and latencies. During both propofol-induced and propofol/remifentanil-induced sedation, the N100 amplitude decreased similarly without an effect on the latencies as the level of sedation increased from Ramsay score 2 to Ramsay score 4 (P < 0.01). At the same clinical level of sedation, propofol plasma concentrations were larger when sedation was achieved by propofol alone (propofol versus propofol/remifentanil, RS 3: 2.12 &mgr;g/mL ± 0.51 versus 1.32 ± 0.43, P < 0.01; RS 4: 3.37 ± 0.47 versus 1.86 ± 0.34, P < 0.01). Our results suggest that long latency auditory evoked potentials provide an objective electrophysiological analog to the clinical assessment of sedation independent of the sedation regime used.

The effects of dexmedetomidine/remifentanil and midazolam/remifentanil on auditory-evoked potentials and electroencephalogram at light-to-moderate sedation levels in healthy subjects.

Avoidance of excessively deep sedation levels is problematic in intensive care patients. Electrophysiologic monitoring may offer an approach to solving this problem. Since electroencephalogram (EEG) responses to different sedation regimens vary, we assessed electrophysiologic responses to two sedative drug regimens in 10 healthy volunteers. Dexmedetomidine/remifentanil (dex/remi group) and midazolam/remifentanil (mida/remi group) were infused 7 days apart. Each combination of medications was given at stepwise intervals to reach Ramsay scores (RS) 2, 3, and 4. Resting EEG, bispectral index (BIS), and the N100 amplitudes of long-latency auditory-evoked potentials (ERP) were recorded at each level of sedation. During dex/remi, resting EEG was characterized by a recurrent high-power low-frequency pattern which became more pronounced at deeper levels of sedation. BIS Index decreased uniformly in only the dex/remi group (from 94 ± 3 at baseline to 58 ± 14 at RS 4) compared to the mida/remi group (from 94 ± 2 to 76 ± 10; P = 0.029 between groups). The ERP amplitudes decreased from 5.3 ± 1.3 at baseline to 0.4 ± 1.1 at RS 4 (P = 0.003) in only the mida/remi group. We conclude that ERPs in volunteers sedated with dex/remi, in contrast to mida/remi, indicate a cortical response to acoustic stimuli, even when sedation reaches deeper levels. Consequently, ERP can monitor sedation with midazolam but not with dexmedetomidine. The reverse is true for BIS.

Auditory event-related potentials, bispectral index, and entropy for the discrimination of different levels of sedation in intensive care unit patients

BACKGROUND:Sedation protocols, including the use of sedation scales and regular sedation stops, help to reduce the length of mechanical ventilation and intensive care unit stay. Because clinical assessment of depth of sedation is labor-intensive, performed only intermittently, and interferes with sedation and sleep, processed electrophysiological signals from the brain have gained interest as surrogates. We hypothesized that auditory event-related potentials (ERPs), Bispectral Index® (BIS), and Entropy® can discriminate among clinically relevant sedation levels. METHODS:We studied 10 patients after elective thoracic or abdominal surgery with general anesthesia. Electroencephalogram, BIS, state entropy (SE), response entropy (RE), and ERPs were recorded immediately after surgery in the intensive care unit at Richmond Agitation-Sedation Scale (RASS) scores of −5 (very deep sedation), −4 (deep sedation), −3 to −1 (moderate sedation), and 0 (awake) during decreasing target-controlled sedation with propofol and remifentanil. Reference measurements for baseline levels were performed before or several days after the operation. RESULTS:At baseline, RASS −5, RASS −4, RASS −3 to −1, and RASS 0, BIS was 94 [4] (median, IQR), 47 [15], 68 [9], 75 [10], and 88 [6]; SE was 87 [3], 46 [10], 60 [22], 74 [21], and 87 [5]; and RE was 97 [4], 48 [9], 71 [25], 81 [18], and 96 [3], respectively (all P < 0.05, Friedman Test). Both BIS and Entropy had high variabilities. When ERP N100 amplitudes were considered alone, ERPs did not differ significantly among sedation levels. Nevertheless, discriminant ERP analysis including two parameters of principal component analysis revealed a prediction probability PK value of 0.89 for differentiating deep sedation, moderate sedation, and awake state. The corresponding PK for RE, SE, and BIS was 0.88, 0.89, and 0.85, respectively. CONCLUSIONS:Neither ERPs nor BIS or Entropy can replace clinical sedation assessment with standard scoring systems. Discrimination among very deep, deep to moderate, and no sedation after general anesthesia can be provided by ERPs and processed electroencephalograms, with similar PKs. The high inter- and intraindividual variability of Entropy and BIS precludes defining a target range of values to predict the sedation level in critically ill patients using these parameters. The variability of ERPs is unknown.

Optical properties of rabbit brain in the red and near-infrared: changes observed under in vivo, postmortem, frozen, and formalin-fixated conditions

Abstract. The outcome of light-based therapeutic approaches depends on light propagation in biological tissues, which is governed by their optical properties. The objective of this study was to quantify optical properties of brain tissue in vivo and postmortem and assess changes due to tissue handling postmortem. The study was carried out on eight female New Zealand white rabbits. The local fluence rate was measured in the VIS/NIR range in the brain in vivo, just postmortem, and after six weeks’ storage of the head at −20°C or in 10% formaldehyde solution. Only minimal changes in the effective attenuation coefficient μeff were observed for two methods of sacrifice, exsanguination or injection of KCl. Under all tissue conditions, μeff decreased with increasing wavelengths. After long-term storage for six weeks at −20°C, μeff decreased, on average, by 15 to 25% at all wavelengths, while it increased by 5 to 15% at all wavelengths after storage in formaldehyde. We demonstrated that μeff was not very sensitive to the method of animal sacrifice, that tissue freezing significantly altered tissue optical properties, and that formalin fixation might affect the tissue’s optical properties.

Comparison of non-calibrated pulse-contour analysis with continuous thermodilution for cardiac output assessment in patients with induced hypothermia after cardiac arrest

AIM Induced mild hypothermia after cardiac arrest interferes with clinical assessment of the cardiovascular status of patients. In this situation, non-invasive cardiac output measurement could be useful. Unfortunately, arterial pulse contour is altered by temperature, and the performance of devices using arterial blood pressure contour analysis to derive cardiac output may be insufficient. METHODS Mild hypothermia (32-34°C) was induced in eight patients after out-of-hospital cardiac arrest and successful resuscitation. Cardiac output (CO) was measured simultaneously by continuous thermodilution using a pulmonary artery catheter and a cardiac output monitor (Vigilance II, Edwards Lifesciences) and by pulse contour analysis using an arterial line and the Vigileo monitor (Edwards Lifesciences) during both normothermia (>36°C) and hypothermia. Continuous CO from both monitors was compared (Bland-Altman) and concordance of changes measured in consecutive 8-min intervals was measured. RESULTS Mean cardiac output was 3.9±1.2 l/min during hypothermia and 6.1±2.6 l/min during normothermia (p<0.001). During hypothermia (normothermia), bias was 0.23 (0.77)l/min, precision (1 SD) was 0.6 (0.72) l/min, and the limits of agreement were -1.06 to 1.51 (-0.64 to 2.18) l/min, corresponding to a percentage error of ±34% (±24%). Concordance of directional CO changes >10% was 53.9% in hypothermia and 51.4% in normothermia. CONCLUSION Induced hypothermia was not associated with increased bias or limits of agreement for the comparison of Vigileo and continuous thermodilution, but percentage error was high during normothermia and increased further during hypothermia. Less than 50% of clinically relevant CO changes during hypothermia were concordant.

Effect of PEEP, blood volume, and inspiratory hold maneuvers on venous return.

According to Guytons model of circulation, mean systemic filling pressure (MSFP), right atrial pressure (RAP), and resistance to venous return (RVR) determine venous return. MSFP has been estimated from inspiratory hold-induced changes in RAP and blood flow. We studied the effect of positive end-expiratory pressure (PEEP) and blood volume on venous return and MSFP in pigs. MSFP was measured by balloon occlusion of the right atrium (MSFPRAO), and the MSFP obtained via extrapolation of pressure-flow relationships with airway occlusion (MSFPinsp_hold) was extrapolated from RAP/pulmonary artery flow (QPA) relationships during inspiratory holds at PEEP 5 and 10 cmH2O, after bleeding, and in hypervolemia. MSFPRAO increased with PEEP [PEEP 5, 12.9 (SD 2.5) mmHg; PEEP 10, 14.0 (SD 2.6) mmHg, P = 0.002] without change in QPA [2.75 (SD 0.43) vs. 2.56 (SD 0.45) l/min, P = 0.094]. MSFPRAO decreased after bleeding and increased in hypervolemia [10.8 (SD 2.2) and 16.4 (SD 3.0) mmHg, respectively, P < 0.001], with parallel changes in QPA Neither PEEP nor volume state altered RVR (P = 0.489). MSFPinsp_hold overestimated MSFPRAO [16.5 (SD 5.8) vs. 13.6 (SD 3.2) mmHg, P = 0.001; mean difference 3.0 (SD 5.1) mmHg]. Inspiratory holds shifted the RAP/QPA relationship rightward in euvolemia because inferior vena cava flow (QIVC) recovered early after an inspiratory hold nadir. The QIVC nadir was lowest after bleeding [36% (SD 24%) of preinspiratory hold at 15 cmH2O inspiratory pressure], and the QIVC recovery was most complete at the lowest inspiratory pressures independent of volume state [range from 80% (SD 7%) after bleeding to 103% (SD 8%) at PEEP 10 cmH2O of QIVC before inspiratory hold]. The QIVC recovery thus defends venous return, possibly via hepatosplanchnic vascular waterfall.

Impact of early-onset seizures on grading and outcome in patients with subarachnoid hemorrhage.

OBJECT After subarachnoid hemorrhage (SAH), seizure occurs in up to 26% of patients. The impact of seizure on outcome has been studied, yet its impact on grading is unknown. The authors evaluated the impact of early-onset seizures (EOS) on grading of spontaneous SAH and on outcome. METHODS This retrospective analysis included consecutive patients with SAH who were treated at the NeuroCenter, Inselspital, University Hospital Bern, Switzerland, between January 2005 and December 2010. Demographic data, clinical data, and reports of EOS were recorded. The EOS were defined as seizures occurring within 24 hours after ictus. Patients were graded according to the World Federation of Neurosurgical Societies (WFNS) scale pre- and postresuscitation and dichotomized into good (WFNS I-III) and poor (WFNS IV-V) grades. Outcome was assessed at 6 months by using the modified Rankin Scale (mRS); an mRS score of 0-3 was considered a good outcome and an mRS score of 4-6 was considered a poor outcome. RESULTS Forty-one of 425 patients with SAH had EOS. Twenty-seven of those 41 patients (65.9%) had a poor WFNS grade. Twenty-eight (68.3%) achieved a good outcome, 11 (26.8%) had a poor outcome, and 2 (4.9%) were lost to followup. Early-onset seizures were proven in 9 of 16 electroencephalograms. The EOS were associated with poor WFNS grade (OR 2.81, 97.5% CI 1.14-7.46; p=0.03) and good outcome (OR 4.01, 97.5% CI 1.63-10.53; p=0.03). Increasing age, hydrocephalus, intracerebral hemorrhage, and intraventricular hemorrhage were associated with poor WFNS grade, whereas only age, intracerebral hemorrhage (p<0.001), and poor WFNS grade (p<0.001) were associated with poor outcome. CONCLUSIONS Patients with EOS were classified significantly more often in a poor grade initially, but then they significantly more often achieved a good outcome. The authors conclude that EOS can negatively influence grading. This might influence decision making for the care of patients with SAH, so grading of patients with EOS should be interpreted with caution.