Intraoperative reduction of vasopressors using processed electroencephalographic monitoring in patients undergoing elective cardiac surgery: a randomized clinical trial.

Intraoperative vasopressor and fluid application are common strategies against hypotension. Use of processed electroencephalographic monitoring (pEEG) may reduce vasopressor application, a known risk factor for organ dysfunction, in elective cardiac surgery patients. Randomized single-centre clinical trial at Jena University Hospital. Adult patients operated on cardiopulmonary bypass or off-pump coronary artery bypass grafting were randomised to receive anesthesia with visible or blinded pEEG using Narcotrend™. In blinded-Narcotrend (NT) depth of anesthesia was extrapolated from clinical signs, hemodynamic response and anesthetic concentration, supplemented by target indices between 37 and 64 in the visible-NT group. Intraoperative norepinephrine requirement (primary endpoint), fluid balance, extubation time, delirium occurrence and adverse events were evaluated. Patients of the intent-to-treat population (visible-NT: n = 123, blinded-NT: n = 122) had similar patient and procedural characteristics. Adjusted for type of surgery intraoperative Norepinephrine application was significantly reduced in visible-NT (n = 120, robust mean of cumulative dose 4.71 µg/kg bodyweight) compared to blinded-NT patients (n = 119, 6.14 µg/kg bodyweight) (adjusted robust mean difference 1.71 (95% CI 0.33-3.10) µg/kg bodyweight). Although reduction in patients operated on cardiopulmonary bypass was higher the interaction was not significant in post-hoc subgroup analysis. Intraoperative fluid balance was similar among both groups and strata. Extubation time was non-significantly lower in visible than in blinded-NT group. Overall postoperative delirium risk was 16.4% without differences among the groups. Adverse events-sudden movement/coughing, perspiration or hypertension-occurred more often with visible-NT, while one blinded-NT patient experienced intraoperative awareness. Titration of depth of anesthesia in elective cardiac surgery patients using pEEG allows to reduce application of norepinephrine.

Pre-procedure ultrasound increases the success and safety of central venous catheterization†.

BACKGROUND: Real-time ultrasound (US) in central venous catheterization is superior to pre-procedure US. However, moving real-time US into routine practice is impeded by its perceived expense and difficulty. Currently, pre-procedure US and landmark (LM) methods are most widely used. We investigated these techniques in internal jugular vein (IJV) catheterization in respect of operator experience, complications, and risk factors. METHODS: In an observational non-randomized study, we investigated 606 of ∼1300 procedures, that is, 200 patients were treated under pre-procedure US and 406 under LM [pathfinder (PF) n=202, direct cannulation (DC) n=204]. We recorded first needle pass success rate, success rate after the third attempt, and the cannulation time. Procedures were performed by inexperienced (<100) or experienced (>100 catheterizations) operators. RESULTS: Pre-procedure US was associated with more successful attempts and shorter cannulation times. Under pre-procedure US, 88% of first attempts were successful and 100% of third attempts. The median (range) cannulation time was 39 (10-330) s. Under PF, only 56% of first, and 87% of third, attempts were successful with a median (range) cannulation time of 100 (25-3600) s. Under DC, 61% of first and 89% of third attempts were successful; the median (range) cannulation time was 70 (10-3600) s. Remarkably, inexperienced operators using pre-procedure US (n=38) were significantly faster than experienced operators using PF or DC (n=343) (cannulation time: median 60 s, range 12-330, for inexperienced; 60 s, range 10-3600, for experienced). First puncture success rates were higher (pre-procedure US, inexperienced 84%, PF or DC, experienced 57%). CONCLUSIONS: Pre-procedure US for IJV catheterization is safe, quick, and superior to LM.

Time-variant partial directed coherence in analysis of the cardiovascular system. A methodological study.

Time-variant partial directed coherence (tvPDC) is used for the first time in a multivariate analysis of heart rate variability (HRV), respiratory movements (RMs) and (systolic) arterial blood pressure. It is shown that respiration-related HRV components which also occur at other frequencies besides the RM frequency (= respiratory sinus arrhythmia, RSA) can be identified. These additional components are known to be an effect of the 'half-the-mean-heart-rate-dilemma' ('cardiac aliasing' CA). These CA components may contaminate the entire frequency range of HRV and can lead to misinterpretation of the RSA analysis. TvPDC analysis of simulated and clinical data (full-term neonates and sedated patients) reveals these contamination effects and, in addition, the respiration-related CA components can be separated from the RSA component and the Traube-Hering-Mayer wave. It can be concluded that tvPDC can be beneficially applied to avoid misinterpretations in HRV analyses as well as to quantify partial correlative interaction properties between RM and RSA.

Positive end-expiratory pressure does not affect indocyanine green plasma disappearance rate or gastric mucosal perfusion after cardiac surgery.

BACKGROUND AND OBJECTIVE: Positive end-expiratory pressure (PEEP) may affect hepato-splanchnic blood flow. We studied whether a PEEP of 10 mbar may negatively influence flow-dependent liver function (indocyanine green plasma disappearance rate, ICG-PDR) and splanchnic microcirculation as estimated by gastric mucosal PCO2 (PRCO2). METHODS: In a randomized, controlled clinical study, we enrolled 28 patients after elective cardiac surgery using cardiopulmonary bypass. In 14 patients (13 male, 1 female; age 48-74, mean 63 +/- 7 yr) we assessed ICG-PDR and PRCO2 on intensive care unit admission with PEEP 5 mbar, after 2 h with PEEP of 10 mbar and again after 2 h at PEEP 5 mbar. Inspiratory peak pressure was adjusted to maintain normocapnia. Fourteen other patients (8 male, 6 female; age 46-86, mean 68 +/- 11 yr) in whom PEEP was 5 mbar throughout served as controls. All patients underwent haemodynamic monitoring by measurement of central venous pressure, left atrial pressure and cardiac index using pulmonary artery thermodilution. RESULTS: While doses of vasoactive drugs and cardiac filling pressures did not change significantly, cardiac index slightly increased in both groups. ICG-PDR remained unchanged either within or between both groups (PEEP10 group: 24.0 +/- 6.9, 22.0 +/- 7.9 and 25.5 +/- 7.7% min-1 vs. controls: 22.0 +/- 7.5, 23.8 +/- 8.4 and 21.4 +/- 6.5% min-1) (P = 0.05). The difference between PRCO2 and end-tidal PCO2 (PCO2-gap) did not change significantly (PEEP10 group: 1.1 +/- 0.9, 1.3 +/- 0.7 and 1.3 +/- 0.9 kPa vs. controls: 0.8 +/- 0.5, 0.9 +/- 0.5 and 0.9 +/- 0.5 kPa). CONCLUSION: A PEEP of 10 mbar for 2 h does not compromise liver function and gastric mucosal perfusion in patients after cardiac surgery with maintained cardiac output.

Increasing cardiac output by fluid loading: effects on indocyanine green plasma disappearance rate and splanchnic microcirculation.

BACKGROUND: Sufficient cardiac pre-load for maintaining adequate cardiac output is a major goal in the treatment of critically ill patients. We studied the effects of increasing cardiac output by fluid loading on the indocyanine green plasma disappearance rate (ICG-PDR) and gastric mucosal regional CO2 tension (PRco2) as an indicator of splanchnic microcirculation. METHODS: With approval by our ethics committee and written consent, we studied post-operatively 12 patients (1 female, 11 males; 66 +/- 13 years) with elective coronary artery bypass grafting (n = 10) or aortic valve replacement (n = 2). All patients had received pulmonary artery and left atrial catheterization previously for clinical indications. Cardiac output and filling pressures were measured immediately after intensive care unit (ICU) admission and 1 h after the beginning of fluid loading. RESULTS: Overall, 630 +/- 130 ml of 6% hydroxyethylstarch (130 kDa) was infused with the splanchnic perfusion pressure remaining constant. Norepinephrine and epinephrine dosages were unchanged. The cardiac index increased significantly from 2.8 +/- 0.7 to 3.5 +/- 0.6 l/min/m2 and the stroke volume index from 30 +/- 7 to 38 +/- 8 ml/m2. ICG-PDR showed no significant change, i.e. from 21.2 +/- 6.5 to 21.6 +/- 6.5%/min. Gastric mucosal PRco2 and the Pco2 gap (difference between regional and end-tidal CO2 tension) were constant, i.e. changed from 5.1 +/- 0.8 to 5.5 +/- 1.1 kPa and from 0.9 +/- 0.5 to 1.0 +/- 0.7 kPa, respectively. CONCLUSION: Increasing cardiac output to supranormal values by fluid loading is not associated with a significant change in ICG-PDR or gastric mucosal PRco2.

Time-variant parametric estimation of transient quadratic phase couplings during electroencephalographic burst activity.

OBJECTIVES: Electroencephalographic burst activity characteristic of burst-suppression pattern (BSP) in sedated patients and of burst-interburst pattern (BIP) in the quiet sleep of healthy neonates have similar linear and non-linear signal properties. Strong interrelations between a slow frequency component and rhythmic, spindle-like activities with higher frequencies have been identified in previous studies. Time-varying characteristics of BSP and BIP prevent a definite patternrelated analysis. A continuous estimation of the bispectrum is essential to analyze these patterns. Parametric bispectral approaches provide this opportunity. METHODS: The adaptation of an AR model leads to a parametric bispectrum by using the transfer function of the estimated AR filter. Time-variant parametric bispectral approaches require an estimation of AR parameters which consider higher order moments to preserve phase information. Accordingly, a time-variant parametric estimation of the bispectrum was introduced. Data driven simulations were performed to provide optimal parameters. BSP (12 patients) and BIP (6 neonates) were analyzed using this novel approach. RESULTS: Significant differences in the time course of burst pattern during BSP and burst-like pattern before the onset of BSP could be shown. A rhythmic quadratic phase coupling (period 10 sec) was identified during BIP in all neonates. CONCLUSION: Quadratic phase couplings during BSP increases in the time course depending on depth of sedation. The visually detected burst activity in BIP is only the temporarily observable EEG correlate of a hidden neural process. Time-variant bispectral approaches offer the possibility of a better characterization of underlying neural processes leading to improved diagnostic tools used in clinical routine.

[Modified ECG-guidance for optimal central venous catheter tip positioning. A transesophageal echocardiography controlled study]. / Optimierte Positionierung zentraler Venenkatheter durch eine modifizierte Anwendung der intravasalen Elektrokardiographie. Validierung mithilfe der transösophagealen Echokardiographie.

BACKGROUND: Intraatrial electrocardiography (ECG) is a well-established method for central-venous catheter (CVC) placement and an intraatrial position is assumed, when a significantly increased P-wave is registered. However, an increase in P-wave amplitude also occurs in other positions. Therefore we evaluated CVC tip positioning by means of transesophageal echocardiography (TEE) at a maximum P-wave amplitude. PATIENTS AND METHODS: In this prospective randomized study the right or left internal jugular vein was cannulated with 100 patients in each group and catheter tip positioning was guided by means of ECG. The catheter was fixed at the position of maximum P-wave amplitude and the insertion depth was registered. The relationship of the CVC tip position to the superior edge of the crista terminalis was demonstrated with the help of TEE. RESULTS: In all patients the catheter tip was found +/- 0.5 cm from the superior edge of the crista terminalis at the transition from the superior vena cava to the right atrium. On x-ray control, all catheters ran along the length of the vessel wall of the superior vena cava. CONCLUSIONS: A maximum P-wave is derived even at the entrance to the right atrium. This explains why ECG-guided CVC placement -- based on the largest P-wave amplitude -- consistently resulted in correct positioning of the CVC tip at the transition from the superior vena cava to the right atrium.

The use and safety of transoesophageal echocardiography in the general ICU -- a minireview.

BACKGROUND: The efficacy of transoesophageal echocardiography (TEE) has been evaluated predominantly in medical and cardiac surgical ICUs. This article reviews the pertinent literature and evaluates the impact of TEE in a general surgical ICU. METHODS: Twenty studies on TEE in the ICU were evaluated for complications, indications, diagnostic, therapeutic, and surgical impact on patient management. Diagnostic impact was defined as identification of the underlying cardiovascular pathology, therapeutic impact as changes in patient management and surgical impact as indication for operative procedures. In addition, we reviewed the TEE reports and patient charts of 216 critically ill patients in a 16-bed multidisciplinary surgical ICU at our university hospital, who underwent a TEE for differential diagnosis of hemodynamic instability from July 1995 to December 1998 to assess the impact of TEE on patient management in a general surgical ICU. RESULTS: The diagnostic, therapeutic and surgical impact in a total of 2,508 patients ranged from 44 to 99% (weighted mean 67.2%), 10-69% (36.0%), and 2-29% (14.1%), respectively. The complication rate was 2.6%, with no examination related mortality. In our series in a general surgical ICU, a diagnostic, therapeutic and surgical impact was inferred in 191 (88.4%), 148 (68.5%) and 12 (5.6%) patients, respectively. Adverse effects were observed in 5.6%. CONCLUSION: TEE is safe, well-tolerated and useful in the management of critically ill patients. This applies as well for hemodynamically unstable patients in a general surgical ICU.

Central venous catheters--the inability of 'intra-atrial ECG' to prove adequate positioning.

BACKGROUND: The classic increase in P wave size, known as 'P-atriale', is a widely accepted criterion for determination of proper positioning of central venous catheter tips. Recent transoesophageal echocardiography (TOE) studies did not confirm intra-atrial position despite advancing the central venous catheter further than indicated by ECG guidance. We postulate that the pericardial reflection rather than the entry into the right atrium corresponds to the ECG changes. In order to test our hypothesis we sought to determine the anatomical substrate for the electrical changes in an animal study. Subsequently, a modified version of the study was undertaken in man and is also reported. METHODS: In six juvenile pigs the left external jugular vein and right carotid artery were cannulated. A triple-lumen central venous catheter was positioned by ECG guidance using a Seldinger wire as an exploring electrode. The venous and arterial catheters were suture fixed 2 cm beyond the onset of an increase in P wave size. The corresponding anatomical catheter tip position was determined by open exploration of the vessels and the heart. Subsequently the catheter tip position (during advancement) of a pulmonary artery catheter and the corresponding electrical ECG changes were examined in 10 patients during open chest cardiac surgery. RESULTS: All catheters-arterial and venous, in animals and humans-revealed an increase in size of the P wave as well as the QRS complex. All venous catheters were positioned in the superior vena cava, beyond the pericardial reflection but outside the right atrium. All arterial catheters were positioned in the ascending aorta thus also beyond the pericardial reflection. CONCLUSIONS: The start of an increase in P wave size does not correspond with the entrance of the right atrium. The anatomic equivalent for the electrophysiological changes of the ECG is the pericardial reflection. ECG guidance is unable to distinguish between venous and arterial catheter position.

Left ventricular dysfunction in lethal severe brain injury: impact of transesophageal echocardiography on patient management.

OBJECTIVE: To evaluate the impact of transesophageal echocardiographic (TEE) studies on further patient management and incidence and degree of left ventricular (LV) dysfunction in patients with lethal severe brain injury. DESIGN AND SETTING: Retrospective, clinical study in two surgical intensive care units in a university hospital. PATIENTS: In 51 patients with severe brain injury ultimately leading to brain death, the results of TEE studies were reviewed for evidence of newly developed LV dysfunction (i.e., regional wall motion abnormalities) and its impact on patient management. MEASUREMENTS AND RESULTS: Seven patients (13.7%) had a diminished LV function global (fractional area change <50%). Four of these patients (7.8%) exhibited a severely reduced LV function (fractional area change <35%). Regional wall motion abnormalities and preserved global function were found in eight patients (15.7%). Patient management was altered in all patients with diminished LV function: implementation of advanced hemodynamic monitoring (n=5), institution or adjustment of inotropes and adjustment of fluid management (n=7). In patients exhibiting a severely reduced LV function and deteriorating cardiovascular status, brain death diagnosis was established by one clinical examination in conjunction with laboratory tests, thus shortening the interval required for brain death diagnosis by about 12 h. CONCLUSIONS: Severe LV dysfunction occurred in about 8% of our patients with severe brain injury ultimately leading to brain death. TEE may be helpful in guiding cardiovascular resuscitation ultimately leading to improved organ procurement rates.

[Transesophageal echocardiography and intraoperative management of patients with renal cell carcinoma and rena cava extension]. / TEE bei intracavaler Ausdehnung von Nierenzellkarzinomen. Intraoperatives Management mit transösophagealer Echokardiographie.

OBJECTIVE: To evaluate the role of intraoperative real-time transesophageal echocardiography (TEE) for the anesthetic and surgical management of patients with renal cell carcinoma and vena cava extension. METHODS: Retrospective analysis of the intraoperative application of TEE in a series of 4 patients. RESULTS: Real-time TEE with a multiplane probe allowed visualization of inferior vena cava tumor extensions, accurate assessment of the distal extent of vena cava invasion into hepatic veins and right atrium, monitoring of embolism and evaluation of cardiac preload and function in all patients. CONCLUSION: Intraoperative TEE is a useful adjunct to the anesthetic and surgical management of patients with renal cell carcinoma and vena cava extension.

Time-variant non-linear phase-coupling analysis of EEG burst patterns in sedated patients during electroencephalic burst suppression period.

OBJECTIVES: The quadratic phase-coupling (QPC) within burst patterns during electroencephalic burst suppression has been quantified. METHODS: It can be shown that a QPC exists between the frequency ranges 0-2.5 and 3-7.5 Hz and between the frequency ranges 0-2.5 and 8-12 Hz. By means of time-variant bicoherence analysis, a strong phase-locking between the modulating and the modulated component can be identified. The phase-locking is demonstrable within the first 250 ms after the burst onset and comes up to the maximum between 750 and 1250 ms. RESULTS: The effect is maintained over the whole first part of the burst (2 s) with a decreasing tendency after 1250 ms. All these effects cannot be found in the EEG before entering the burst suppression period (BSP). The transient coupling phenomena in the EEG bursts during BSP can be regarded as indicators for short-term interrelations between the underlying electrophysiologic processes. CONCLUSIONS: It can be suggested that the method introduced for the quantification of the sedation depth should be used.

Short-term dynamics of relative coordination between respiratory movements, heart rate and arterial pressure fluctuations within the respiratory frequency range.

The possible linear short-term coordination between respiratory movements (RESP), heart rate fluctuations (HRF), and arterial blood pressure fluctuations (BPF) in conscious human beings has not yet been investigated because of the restricted time resolution of conventional time series analysis. At present, this short-term dynamics as an expression of relative coordination can be quantified by newly developed adaptive autoregressive modeling of time series using Kalman filtering. Thus, in 6 conscious healthy volunteers, RESP, HRF, and BPF were recorded during 10 min in the supine position, at rest and during paced breathing. A considerable part of calculated ordinary and partial coherence sequences of short-term resolution between RESP and HRF, RESP and BPF, and partially between HRF and BPF showed patterns varying in time that could be correlated to changes between gradual coordinations (coherence changing between 0.40 and 0.95). They were more seldom complete or absent. There were mostly opposite changes between partial coherence sequences RESP-HRF/BPF and RESP-BPF/HRF demonstrating competitive behavior between these coordinations. Paced breathing did not essentially affect any observed characteristics. Therefore, these coherence dynamics are not essentially dependent on voluntary breathing movements. We conclude that to a different extent these linear and changing couplings between RESP, HRF, and BPF in conscious human beings exhibit properties of short-term complete and more frequently gradual coordinations showing dynamics that can not be determined by conventional methods.

Atropine test and circulatory arrest in the fossa posterior assessed by transcranial Doppler.

OBJECTIVE: To evaluate whether a negative atropine test (i.e., increase in heart rate of less than 3% after intravenous administration of 3 mg atropine) correctly predicts circulatory arrest in the fossa posterior during craniocaudal herniation in patients with primary supratentorial lesions. MATERIAL AND METHODS: Prospective, observational clinical study. SETTING: Two surgical intensive care units in a university hospital. PATIENTS: In 45 consecutive patients with suspected brain death, an atropine test (AT) and a transcranial Doppler sonography were performed simultaneously and, if necessary, repeatedly. MEASUREMENTS AND RESULTS: Forty-four patients fulfilled the typical criteria of a supratentorial and infratentorial circulatory arrest as the atropine test became negative. In one patient, who had undergone a decompressive craniectomy for uncontrollable intracranial pressure 4 h prior to the AT testing, we found a negative AT in the presence of an antegrade supratentorial and infratentorial flow. CONCLUSION: A negative atropine test indicates a circulatory arrest in the fossa posterior in patients with primary supratentorial lesions and craniocaudal herniation. In patients with brain-stem lesions, however, a negative atropine test does not unequivocally indicate a circulatory arrest.

Quantification of transient quadratic phase couplings within EEG burst patterns in sedated patients during electroencephalic burst-suppression period.

The time dynamics of the quadratic phase coupling within burst patterns during electroencephalic burst-suppression has been quantified. It can be shown that a transient quadratic phase coupling (QPC) exists between the frequency ranges 0 to 2.5 and 3 to 7.5 Hz and between the frequency ranges 0 to 2.5 and 8 to 12 Hz. The QPC can be explained by an amplitude modulation, where the slow rhythm modulates the rhythmic activities with a higher frequency. By means of time-variant bicoherence analysis, a strong phase-locking between the modulating and the modulated component can be identified. The phase-locking is demonstrable within the first 250 ms after the burst onset and comes up to the maximum between 750 and 1250 ms. The effect is maintained over the whole first part of the burst (2 s) with a decreasing tendency after 1250 ms. All these effects cannot be found in the EEG before entering the burst suppression period (BSP). The transient coupling phenomena in the EEG bursts during BSP can be regarded as indicators for short-term interrelations between the underlying electrophysiologic processes.

Adaptable preprocessing units and neural classification for the segmentation of EEG signals.

In this contribution, a methodology for the simultaneous adaptation of preprocessing units (PPUs) for feature extraction and of neural classifiers that can be used for time series classification is presented. The approach is based upon an extension of the backpropagation algorithm for the correction of the preprocessing parameters. In comparison with purely neural systems, the reduced input dimensionality improves the generalization capability and reduces the numerical effort. In comparison with PPUs with fixed parameters, the success of the adaptation is less sensitive to the choice of the parameters. The efficiency of the developed method is demonstrated via the use of quadratic filters with adaptable transmission bands as preprocessing units for the segmentation of two different types of discontinuous EEG: discontinuous neonatal EEG (burst-interburst segmentation) and EEG in deep stages of sedation (burst-suppression segmentation).

Interrelations between EEG frequency components in sedated intensive care patients during burst-suppression period.

The EEG during basic sedation and burst patterns during electroencephalic burst-suppression patterns (BSP) were analyzed. The aim of EEG analysis was the characterization and quantification of the interrelations between distinct frequency components in both states of sedation. The data for the investigations were derived from the routine EEG derivations of 12 patients with various neurosurgical diseases. It can be demonstrated that the degree of interrelation (amplitude modulation) between a low-frequency component (0-2.5 Hz) and oscillations with higher frequency (3-7.5 and 8-12 Hz) is increased in burst patterns during BSP compared with the EEG during basic sedation. It can be concluded that the degree of interrelations depends on the sedation depth induced by hypnotic drugs.

New approaches for the detection and analysis of electroencephalographic burst-suppression patterns in patients under sedation.

An automatic EEG pattern detection unit was developed and tested for the recognition of burst-suppression periods and for the separation of burst from suppression patterns. The median, standard deviation and the 95% edge frequency were computed from single channels of the EEG within a moving window and completed by the continuous computation of frequency band power via an adapted Hilbert resonance filter. These parameters were given to the inputs of two hierarchically arranged artificial neural networks (NNs). The output signals of NNs indicate the suppression and burst phases. The burst recognition was focused on the precise recognition of the burst onset. In subsequent processing steps the time course of percentages of burst patterns within their corresponding burst-suppression-phases was calculated and the time locations of burst onsets can be used to trigger an averaging for a burst-related analysis. The data for our investigations were derived from the routine EEG derivations of 12 patients with various neurosurgical diseases. A group-related training of the NNs was realized. For the group-related trained NNs EEG data for 6 patients were used for training and the data of 6 other patients for testing the classification performance of the pattern recognition units. Additionally, the reliability of the detection algorithm was tested with data of two patients with convulsive state, resistant to treatment, and burst-suppression like pattern EEC.