Cornelia Genbrugge

An observational near-infrared spectroscopy study on cerebral autoregulation in post-cardiac arrest patients: Time to drop ‘one-size-fits-all’ hemodynamic targets?

AIMS A subgroup of patients with ROSC after cardiac arrest (CA) with disturbed cerebral autoregulation might benefit from higher mean arterial pressures (MAP). We aimed to (1) phenotype patients with disturbed autoregulation, (2) investigate whether these patients have a worse prognosis, (3) define an individual optimal MAP per patient and (4) investigate whether time under this individual optimal MAP is associated with outcome. METHODS Prospective observational study in 51 post-CA patients monitored with near infrared spectroscopy. RESULTS (1) 18/51 patients (35%) had disturbed autoregulation. Phenotypically, a higher proportion of patients with disturbed autoregulation had pre-CA hypertension (31±47 vs. 65±49%, p=0.02) suggesting that right shifting of autoregulation is caused by chronic adaptation of cerebral blood flow to higher blood pressures. (2) In multivariate analysis, patients with preserved autoregulation (n=33, 65%) had a significant higher 180-days survival rate (OR 4.62, 95% CI [1.06:20.06], p=0.04]. Based on an index of autoregulation (COX), the average COX-predicted optimal MAP was 85 mmHg in patients with preserved and 100 mmHg in patients with disturbed autoregulation. (3) An individual optimal MAP could be determined in 33/51 patients. (4) The time under the individual optimal MAP was negatively associated with survival (OR 0.97, 95% CI [0.96:0.99], p=0.02). The time under previously proposed fixed targets (65, 70, 75, 80 mmHg) was not associated with a differential survival rate. CONCLUSION Cerebral autoregulation showed to be disturbed in 35% of post-CA patients of which a majority had pre-CA hypertension. Disturbed cerebral autoregulation within the first 24h after CA is associated with a worse outcome. In contrast to uniform MAP goals, the time spent under a patient tailored optimal MAP, based on an index of autoregulation, was negatively associated with survival.

Hemodynamic targets during therapeutic hypothermia after cardiac arrest: A prospective observational study ☆

AIM In analogy with sepsis, current post-cardiac arrest (CA) guidelines recommend to target mean arterial pressure (MAP) above 65 mmHg and SVO2 above 70%. This is unsupported by mortality or cerebral perfusion data. The aim of this study was to explore the associations between MAP, SVO2, cerebral oxygenation and survival. METHODS Prospective, observational study during therapeutic hypothermia (24h - 33 °C) in 82 post-CA patients monitored with near-infrared spectroscopy. RESULTS Forty-three patients (52%) survived in CPC 1-2 until 180 days post-CA. The mean MAP range associated with maximal survival was 76-86 mmHg (OR 2.63, 95%CI [1.01; 6.88], p = 0.04). The mean SVO2 range associated with maximal survival was 67-72% (OR 8.23, 95%CI [2.07; 32.68], p = 0.001). In two separate multivariate models, a mean MAP (OR 3.72, 95% CI [1.11; 12.50], p=0.03) and a mean SVO2 (OR 10.32, 95% CI [2.03; 52.60], p = 0.001) in the optimal range persisted as independently associated with increased survival. Based on more than 1625000 data points, we found a strong linear relation between SVO2 (range 40-90%) and average cerebral saturation (R(2) 0.86) and between MAP and average cerebral saturation for MAPs between 45 and 101 mmHg (R(2) 0.83). Based on our hemodynamic model, the MAP and SVO2 ranges associated with optimal cerebral oxygenation were determined to be 87-101 mmHg and 70-75%. CONCLUSION we showed that a MAP range between 76-86 mmHg and SVO2 range between 67% and 72% were associated with maximal survival. Optimal cerebral saturation was achieved with a MAP between 87-101 mmHg and a SVO2 between 70% and 75%. Prospective interventional studies are needed to investigate whether forcing MAP and SVO2 in the suggested range with additional pharmacological support would improve outcome.

Increase in cerebral oxygenation during advanced life support in out-of-hospital patients is associated with return of spontaneous circulation

IntroductionBy maintaining sufficient cerebral blood flow and oxygenation, the goal of cardiopulmonary resuscitation (CPR) is to preserve the pre-arrest neurological state. To date, cerebral monitoring abilities during CPR have been limited. Therefore, we investigated the time-course of cerebral oxygen saturation values (rSO2) during advanced life support in out-of-hospital cardiac arrest. Our primary aim was to compare rSO2 values during advanced life support from patients with return of spontaneous circulation (ROSC) to patients who did not achieve ROSC.MethodsWe performed an observational study to measure rSO2 using Equanox™ (Nonin, Plymouth, MI) from the start of advanced life support in the pre-hospital setting.ResultsrSO2 of 49 consecutive out-of-hospital cardiac arrest patients were analyzed. The total increase from initial rSO2 value until two minutes before ROSC or end of advanced life support efforts was significantly larger in the group with ROSC 16% (9 to 36) compared to the patients without ROSC 10% (4 to 15) (P = 0.02). Mean rSO2 from the start of measurement until two minutes before ROSC or until termination of advanced life support was higher in patients with ROSC than in those without, namely 39% ± 7 and 31% ± 4 (P = 0.05) respectively.ConclusionsDuring pre-hospital advanced life support, higher increases in rSO2 are observed in patients attaining ROSC, even before ROSC was clinically determined. Our findings suggest that rSO2 could be used in the future to guide patient tailored treatment during cardiac arrest and could therefore be a surrogate marker of the systemic oxygenation state of the patient.

Regional cerebral oximetry during cardiopulmonary resuscitation: useful or useless?

BACKGROUND Approximately 375,000 people annually experience sudden cardiac arrest (CA) in Europe. Most patients who survive the initial hours and days after CA die of postanoxic brain damage. Current monitors, such as electrocardiography and end-tidal capnography, provide only indirect information about the condition of the brain during cardiopulmonary resuscitation (CPR). In contrast, cerebral near-infrared spectroscopy provides continuous, noninvasive, real-time information about brain oxygenation without the need for a pulsatile blood flow. It measures transcutaneous cerebral tissue oxygen saturation (rSO2). This information could supplement currently used monitors. Moreover, an evolution in rSO2 monitoring technology has made it easier to assess rSO2 in CA conditions. OBJECTIVE We give an overview of the literature regarding rSO2 measurements during CPR and the current commercially available devices. We highlight the feasibility of cerebral saturation measurement during CPR, its role as a quality parameter of CPR, predictor of return of spontaneous circulation (ROSC) and neurologic outcome, and its monitoring function during transport. DISCUSSION rSO2 is feasible in the setting of CA and has the potential to measure the quality of CPR, predict ROSC and neurologic outcome, and monitor post-CA patients during transport. CONCLUSION The literature shows that rSO2 has the potential to serve multiple roles as a neuromonitoring tool during CPR and also to guide neuroprotective therapeutic strategies.

Low hemoglobin levels are associated with lower cerebral saturations and poor outcome after cardiac arrest

PURPOSE Post-cardiac arrest (CA) patients have a large cerebral penumbra at risk for secondary ischemic damage in case of suboptimal brain oxygenation during ICU stay. The aims of this study were to investigate the association between hemoglobin, cerebral oxygenation (SctO2) and outcome in post-CA patients. METHODS Prospective observational study in 82 post-CA patients. Hemoglobin, a corresponding SctO2 measured by NIRS and SVO2 in patients with a pulmonary artery catheter (n=62) were determined hourly during hypothermia in the first 24h of ICU stay. RESULTS We found a strong linear relationship between hemoglobin and mean SctO2 (SctO2=0.70×hemoglobin+56 (R(2) 0.84, p=10(-6))). Hemoglobin levels below 10g/dl generally resulted in lower brain oxygenation. There was a significant association between good neurological outcome (43/82 patients in CPC 1-2 at 180 days post-CA) and admission hemoglobin above 13g/dl (OR 2.76, 95% CI 1.09:7.00, p=0.03) or mean hemoglobin above 12.3g/dl (OR 2.88, 95%CI 1.02:8.16, p=0.04). This association was entirely driven by results obtained in patients with a mean SVO2 below 70% (OR 6.25, 95%CI 1.33:29.43, p=0.01) and a mean SctO2 below 62.5% (OR 5.87, 95%CI 1.08:32.00, p=0.03). CONCLUSION Hemoglobin levels below 10g/dl generally resulted in lower cerebral oxygenation. Average hemoglobin levels below 12.3g/dl were associated with worse outcome in patients with suboptimal SVO2 or SctO2. The safety of a universal restrictive transfusion threshold of 7g/dl can be questioned in post-CA patients.

Accuracy of continuous thermodilution cardiac output monitoring by pulmonary artery catheter during therapeutic hypothermia in post-cardiac arrest patients

PURPOSE Thermodilution continuous cardiac output measurements (TDCCO) by pulmonary artery catheter (PAC) have not been validated during therapeutic hypothermia in post-cardiac arrest patients. The calculated cardiac output based on the indirect Fick principle (FCO) using pulmonary artery blood gas mixed venous oxygen saturation (FCO-BG-SvO2) is considered as the gold standard. Continuous SvO2 by PAC (PAC-SvO2) has also not been validated previously during hypothermia. The aims of this study were (1) to compare FCO-BG-SvO2 with TDCCO, (2) to compare PAC-SvO2 with BG-SvO2 and finally (3) to compare FCO with SvO2 obtained via PAC or blood gas. METHODS We analyzed 102 paired TDCCO/FCO-BG-SvO2 and 88 paired BG-SvO2/PAC-SvO2 measurements in 32 post-cardiac arrest patients during therapeutic hypothermia. RESULTS TDCCO was significantly although poorly correlated with FCO-BG-SvO2 (R2 0.21, p<0.01) without systematic bias (-0.15±1.76 l/min). Analysis according to Bland and Altman however showed broad limits of agreement ([-3.61; 3.45] l/min) and an unacceptable high percentage error (105%). None of the criteria for clinical interchangeability were met. Concordance analysis showed that TDCCO had limited trending ability (R2 0.03). FCO based on PAC-SvO2 was highly correlated with FCO-BG-SvO2 (R2 0.72) with a small bias (-0.08±0.72 l/min) and slightly too high percentage error (44%). CONCLUSION Our results show an extreme inaccuracy of TDCCO by PAC in post-cardiac arrest patients during therapeutic hypothermia. We found a reasonable correlation between BG-SvO2 and PAC-SvO2 and subsequently between FCO calculated with SvO2 obtained either via blood gas or PAC. The decision to start or titrate inotropics should therefore not be guided by TDCCO in this setting.

Cerebral saturation monitoring during cardiopulmonary resuscitation should be used as dynamic, rather than static, information

With great interest we read the paper of Parnia et al.1 The uthors report a significantly higher overall mean rSO2 in patients ith return of spontaneous circulation (ROSC) in comparison with on-survivors (respectively 35 ± 5 vs 18 ± 0.4). First of all, both hese values are extremely low, despite the fact that all patients ad in-hospital cardiac arrest, and shorter delays to treatment (and igher overall mean rSO2) are expected compared to patients with ut of hospital arrest.2 The reason for these low values might be elated to the used near-infrared spectroscopy (NIRS) technology INVOS® is a relative O2 saturation monitoring). Secondly, the difference in rSO2 between survivors and nonurvivors is the highest during the final 5 min of resuscitation. This s not a surprising observation, since increasing rSO2 is a precuror of the onset of ROSC and at ROSC, the difference in rSO2 is or sure the greatest compared to rSO2 values in patients who ever had ROSC (and therefore worse hemodynamics without any ncrease in rSO2 during the whole cardiopulmonary resuscitation CPR)). We are not sure whether the slow increase in rSO2 observed efore ROSC might not be explained by the use of a “relative” NIRS echnology (with a proprietary averaging algorithm), not providing absolute” saturation values. The authors confirmed that their findings indicate that rSO2 in ardiac arrest is a dynamic measurement and that any decrease or

Regional cerebral saturation monitoring during withdrawal of life support until death

AIMS The aim of this pilot study was to explore the regional cerebral oxygen saturation (rSO2) during the process of dying in Intensive Care Unit (ICU) patients in whom it was decided to withdraw life support. METHODS Regional cerebral saturation was measured from the moment active treatment was stopped until the moment of death, defined as the onset of asystole. Simultaneously, heart rate and arterial blood pressure were recorded using a radial arterial catheter. Baseline rSO2 values were calculated as mean values over one hour in stable haemodynamic conditions immediately after the decision to withdraw life support. RESULTS Cerebral saturation was measured in six dying ICU patients. The mean age of patients was 64year. The median baseline rSO2 value was 64% (58%-68%). At time of death, median rSO2 was 33% (7%-40%). The median decrease in rSO2 from baseline until death was 31% (25%-45%). The median decrease in rSO2 observed during the last hour before time of death was 20% (12%-31%). CONCLUSION A continuous and patient specific decrease in rSO2 was observed in all patients with a simultaneous decrease in MAP. However, the absolute rSO2 value at moment death was clinically determined, had a broad range, indicating that there is no clear cut-off rSO2 value for death probably due to the heterogeneity of the studied population. Taken together, these observations highlight the importance of following trends and comparing rSO2 values in the cardiac arrest setting.

The validation of simplified EEG derived from the bispectral index monitor in post-cardiac arrest patients

AIMS We aimed to validate retrospectively the accuracy of simplified electroencephalography (EEG) monitoring derived from the bispectral index (BIS) monitor in post-cardiac arrest (CA) patients. METHODS Successfully resuscitated CA patients were transferred to the Catherization Lab followed by percutaneous coronary intervention when indicated. On arrival at the coronary care unit, bilateral BIS monitoring was started and continued up to 72 h. Raw simplified EEG tracings were extracted from the BIS monitor at a time point coinciding with the registration of standard EEG monitoring. BIS EEG tracings were reviewed by two neurophysiologists, who were asked to indicate the presence of following patterns: diffuse slowing rhythm, burst suppression pattern, cerebral inactivity, periodic epileptiform discharges and status epilepticus (SE). Additionally, these simplified BIS EEG tracings were analysed by two inexperienced investigators, who were asked to indicate the presence of SE only. RESULTS Thirty-two simplified BIS EEG samples were analysed. Compared to standard EEG, neurophysiologists interpreted all simplified EEG samples with a sensitivity of 86%, a specificity of 100% and an interobserver variability of 0.843. Furthermore, SE was identified with a sensitivity of 80% and a specificity of 94% by two unexperienced physicians. CONCLUSION Using a simple classification system, raw simplified EEG derived from a BIS monitoring device is comparable to standard EEG monitoring. Moreover, investigators without EEG experience were capable to identify SE in post-CA patients. Future studies will be warranted to confirm our results and to determine the added value of using simplified BIS EEG in terms of prognostic and therapeutic implications.

Non-invasive assessment of cerebral oxygenation: A comparison of retinal and transcranial oximetry

Background To investigate the correlation between cerebral (SO2-transcranial), retinal arterial (SaO2-retinal) and venous (SvO2-retinal) oxygen saturation as measured by near-infrared spectroscopy (NIRS) and retinal oximetry respectively. Methods Paired retinal and cerebral oxygen saturation measurements were performed in healthy volunteers. Arterial and venous retinal oxygen saturation and diameter were measured using a non-invasive spectrophotometric retinal oximeter. Cerebral oxygen saturation was measured using near-infrared spectroscopy. Correlations between SO2-transcranial and retinal oxygen saturation and diameter measurements were assessed using Pearson correlation coefficients. Lin’s concordance correlation coefficient (CCC) and Bland-Altman analysis were performed to evaluate the agreement between SO2-transcranial as measured by NIRS and as estimated using a fixed arterial:venous ratio as 0.3 x SaO2-retinal + 0.7 x SvO2-retinal. The individual relative weight of SaO2-retinal and SvO2-retinal to obtain the measured SO2-transcranial was calculated for all subjects. Results Twenty-one healthy individuals aged 26.4 ± 2.2 years were analyzed. SO2-transcranial was positively correlated with both SaO2-retinal and SvO2-retinal (r = 0.44, p = 0.045 and r = 0.43, p = 0.049 respectively) and negatively correlated with retinal venous diameter (r = -0.51, p = 0.017). Estimated SO2-transcranial based on retinal oximetry showed a tolerance interval of (-13.70 to 14.72) and CCC of 0.46 (95% confidence interval: 0.05 to 0.73) with measured SO2-transcranial. The average relative weights of SaO2-retinal and SvO2-retinal to obtain SO2-transcranial were 0.31 ± 0.11 and 0.69 ± 0.11, respectively. Conclusion This is the first study to show the correlation between retinal and cerebral oxygen saturation, measured by NIRS and retinal oximetry. The average relative weight of arterial and venous retinal oxygen saturation to obtain the measured transcranial oxygen saturation as measured by NIRS, approximates the established arterial:venous ratio of 30:70 closely, but shows substantial inter-individual variation. These findings provide a proof of concept for the role of retinal oximetry in evaluating cerebral oxygenation.