Comparison of the novel membrane-based carbon dioxide filter memsorb™ with a chemical granulate absorbent using a high-fidelity lung simulator: a prospective randomized in vitro trial.

PURPOSE: Memsorb™ is a novel device for carbon dioxide (CO2) removal from anesthesia circuits via a semipermeable polymeric membrane. We evaluated the performance of the memsorb device for the removal of CO2 in an Aisys™ CS2 machine and compared it with a standard chemical granulate absorber (CGA) using a high-fidelity lung simulator. METHODS: We used an in vitro lung simulator (DUCt) to control CO2 release by imitating alveolar gas exchange. The ventilator settings were identical for all measurements. The fresh gas flow (FGF) was randomized to either 0.5 L·min-1 or 2 L·min-1, completing three trials for each FGF for either memsorb or CGA. The EtCO2 and FICO2 levels were recorded for 30 min in each setting. RESULTS: EtCO2 was comparable between the groups with 2 L·min-1 FGF over the observation period. FICO2 was significantly higher in the memsorb group during the trial (2 L·min-1; 3.9 mm Hg; 95% CI, 4.4 to 3.3; P < 0.001). EtCO2 with 0.5 L·min-1 FGF was higher with memsorb than with CGA over the observation period (3.7 mm Hg; 95% CI, 2.7 to 4.7; P = 0.004). With 0.5 L·min-1 FGF, FICO2 was significantly higher in the memsorb group compared with CGA over the whole observation period (6 mm Hg; 95% CI, 6.4 to 5.5; P < 0.001). DISCUSSION: CO2 was successfully removed from the anesthesia circuit. FICO2 was significantly higher with memsorb throughout the observation period. Nevertheless, the clinical impact of these observations remains unclear. Further clinical trials are required to determine the utility of the novel device.

RéSUMé: OBJECTIF: Le memsorb™ est un nouveau dispositif pour l'élimination du dioxyde de carbone (CO2) des circuits d'anesthésie par une membrane polymère semi-perméable. Nous avons évalué la performance du dispositif memsorb pour éliminer le CO2 dans une machine d'anesthésie Aisys™ CS2 et l'avons comparé à la chaux sodée standard en utilisant un simulateur pulmonaire haute fidélité. MéTHODE: Nous avons utilisé un simulateur pulmonaire (DUCt) in vitro pour contrôler la libération de CO2 en imitant l'échange gazeux alvéolaire. Les réglages du ventilateur étaient identiques pour toutes les mesures. Le débit de gaz frais (DGF) a été randomisé à 0,5 L·min−1 ou 2 L·min−1, complétant trois essais pour chaque DGF pour le memsorb ou la chaux sodée. Les taux d'EtCO2 et de FICO2 ont été enregistrés pendant 30 minutes dans chaque réglage. RéSULTATS: Les valeurs d'EtCO2 était comparables entre les groupes avec un DGF à 2 L·min−1 au cours de la période d'observation. La FICO2 était significativement plus élevée avec le MEMsorb pendant l'essai (2 L·min−1; 3,9 mm Hg; IC 95 %, 4,4 à 3,3; P < 0,001). À un DGF 0,5 L·min−1, l'EtCO2 était plus élevé avec le memsorb qu'avec la chaux sodée au cours de la période d'observation (3,7 mm Hg; IC 95 %, 2,7 à 4,7; P = 0,004). À un DGF de 0,5 L·min−1, la FICO2 était significativement plus élevée avec le MEMsorb par rapport à la chaux sodée sur l'ensemble de la période d'observation (6 mm Hg; IC 95 %, 6,4 à 5,5; P < 0,001). DISCUSSION: Le CO2 a bien été éliminé du circuit d'anesthésie. La FICO2 était significativement plus élevée avec le MEMsorb tout au long de la période d'observation. Néanmoins, l'impact clinique de ces observations reste incertain. D'autres études cliniques sont nécessaires pour déterminer l'utilité du nouveau dispositif.

Learning curve and performance in simulated difficult airway for the novel C-MAC® video-stylet and C-MAC® Macintosh video laryngoscope: A prospective randomized manikin trial.

Difficult airways can be managed with a range of devices, with video laryngoscopes (VLs) being the most common. The C-MAC® Video-Stylet (VS; Karl-Storz Germany), a hybrid between a flexible and a rigid intubation endoscope, has been recently introduced. The aim of this study is to investigate the performance of the VS compared to a VL (C-MAC Macintosh blade, Karl-Storz Germany) with regards to the learning curve for each device and its ability to manage a simulated difficult airway manikin. This is a single-center, prospective, randomized, crossover study involving twenty-one anesthesia residents performing intubations on a Bill 1™ (VBM, Germany) airway manikin model. After a standardized introduction, six randomized attempts with VL and VS were performed on the manikin. This was followed by intubation in a simulated difficult airway (cervical collar and inflated tongue) with both devices in a randomized fashion. The primary end-point of this study was the total time to intubation. All continuous variables were expressed as the median [interquartile range] and analyzed using the Mann-Whitney U test. A 2-way ANOVA with Bonferroni's post hoc test was used to compare both devices at each trial. All reported p values are two sided. The median total time to intubation on a simulated difficult airway was faster with the VS compared to VL (17 [13.5-25] sec vs 23 [18.5-26.5] sec, respectively; 95% CI; P = 0.031). Additionally, on a normal airway manikin, the VS has a comparable learning curve to the VL. In this manikin-based study, the novel VS was comparable to the VL in terms of learning curve in a normal airway. In a simulated difficult airway, the total time to intubation, though likely not clinically relevant, was faster with the VS to the VL. However, given the above findings, this study justifies further human clinical trials with the VS to see if similar benefits-faster time to intubation and similar learning curve to VL-are replicated clinically.

Anesthesiology and cognitive impairment: a narrative review of current clinical literature.

BACKGROUND: The impact of general anesthesia on cognitive impairment is controversial and complex. A large body of evidence supports the association between exposure to surgery under general anesthesia and development of delayed neurocognitive recovery in a subset of patients. Existing literature continues to debate whether these short-term effects on cognition can be attributed to anesthetic agents themselves, or whether other variables are causative of the observed changes in cognition. Furthermore, there is conflicting data on the relationship between anesthesia exposure and the development of long-term neurocognitive disorders, or development of incident dementia in the patient population with normal preoperative cognitive function. Patients with pre-existing cognitive impairment present a unique set of anesthetic considerations, including potential medication interactions, challenges with cooperation during assessment and non-general anesthesia techniques, and the possibility that pre-existing cognitive impairment may impart a susceptibility to further cognitive dysfunction. MAIN BODY: This review highlights landmark and recent studies in the field, and explores potential mechanisms involved in perioperative cognitive disorders (also known as postoperative cognitive dysfunction, POCD). Specifically, we will review clinical and preclinical evidence which implicates alterations to tau protein, inflammation, calcium dysregulation, and mitochondrial dysfunction. As our population ages and the prevalence of Alzheimer's disease and other forms of dementia continues to increase, we require a greater understanding of potential modifiable factors that impact perioperative cognitive impairment. CONCLUSIONS: Future research should aim to further characterize the associated risk factors and determine whether certain anesthetic approaches or other interventions may lower the potential risk which may be conferred by anesthesia and/or surgery in susceptible individuals.

Use of the Novel C-MAC Video Stylet in a Case of Predicted Difficult Intubation: A Case Report.

Video laryngoscopes are commonly used to manage difficult airways, among other devices. However, they present a challenge when inserting the blade in patients with a limited mouth opening, and an adequate visualization of the glottis does not always translate into successful intubation. The C-MAC Video-Stylet-with its small diameter and flexible tip-offers an effective alternative. We describe the successful use of the novel C-MAC Video-Stylet to secure the airway in a patient with minimal mouth opening due to the side effects of previous neck surgery and radiation therapy.

Using King Vision video laryngoscope with a channeled blade prolongs time for tracheal intubation in different training levels, compared to non-channeled blade.

PURPOSE: It is generally accepted that using a video laryngoscope is associated with an improved visualization of the glottis. However, correctly placing the endotracheal tube might be challenging. Channeled video laryngoscopic blades have an endotracheal tube already pre-loaded, allowing to advance the tube once the glottis is visualized. We hypothesized that use of a channel blade with pre-loaded endotracheal tube results in a faster intubation, compared to a curved Macintosh blade video laryngoscope. METHODS: After ethical approval and informed consent, patients were randomized to receive endotracheal Intubation with either the King Vision® video laryngoscope with curved blade (control) or channeled blade (channeled). Success rate, evaluation of the glottis view (percentage of glottic opening (POGO), Cormack&Lehane (C&L)) and intubating time were evaluated. RESULTS: Over a two-month period, a total of 46 patients (control n = 23; channeled n = 23) were examined. The first attempt success rates were comparable between groups (control 100% (23/23) vs. channeled 96% (22/23); p = 0.31). Overall intubation time was significantly shorter with control (median 40 sec; IQR [24-58]), compared to channeled (59 sec [40-74]; p = 0.03). There were no differences in glottis visualization between groups. CONCLUSION: Compared with the King Vision channeled blade, time for tracheal intubation was shorter with the control group using a non-channeled blade. First attempt success and visualization of the glottis were comparable. These data do not support the hypothesis that a channeled blade is superior to a curved video laryngoscopic blade without tube guidance. TRIAL REGISTRATION: ClinicalTrials.gov NCT02344030.

Evaluation of the McGrath MAC and Macintosh laryngoscope for tracheal intubation in 2000 patients undergoing general anaesthesia: the randomised multicentre EMMA trial study protocol.

INTRODUCTION: The direct laryngoscopy technique using a Macintosh blade is the first choice globally for most anaesthetists. In case of an unanticipated difficult airway, the complication rate increases with the number of intubation attempts. Recently, McGrath MAC (McGrath) video laryngoscopy has become a widely accepted method for securing an airway by tracheal intubation because it allows the visualisation of the glottis without a direct line of sight. Several studies and case reports have highlighted the benefit of the video laryngoscope in the visualisation of the glottis and found it to be superior in difficult intubation situations. The aim of this study was to compare the first-pass intubation success rate using the (McGrath) video laryngoscope compared with conventional direct laryngoscopy in surgical patients. METHODS AND ANALYSIS: The EMMA trial is a multicentre, open-label, patient-blinded, randomised controlled trial. Consecutive patients requiring tracheal intubation are randomly allocated to either the McGrath video laryngoscope or direct laryngoscopy using the Macintosh laryngoscope. The expected rate of successful first-pass intubation is 95% in the McGrath group and 90% in the Macintosh group. Each group must include a total of 1000 patients to achieve 96% power for detecting a difference at the 5% significance level. Successful intubation with the first attempt is the primary endpoint. The secondary endpoints are the time to intubation, attempts for successful intubation, the necessity of alternatives, visualisation of the glottis using the Cormack & Lehane score and percentage of glottic opening score and definite complications. ETHICS AND DISSEMINATION: The project was approved by the local ethics committee of the Medical Association of the Rhineland Palatine state and Westphalia-Lippe. The results of this study will be made available in the form of manuscripts for publication and presentations at national and international meetings. TRIAL REGISTRATION NUMBER: ClinicalTrials.gov NCT 02611986; pre-results.

Evaluation of the optimal cuff volume and cuff pressure of the revised laryngeal tube "LTS-D" in surgical patients.

BACKGROUND: Recent case reports have indicated significant cuff overinflation when using the standard filling volume based on the manufacturer's recommendations in older models of laryngeal tubes. The aim of this study was to determine the minimum cuff pressure needed to perform standardized ventilation without leakage in the new, revised model of the laryngeal tube "LTS-D". METHODS: After ethical approval, LTS-D was placed for ventilation in 60 anesthetized patients. The cuff was inflated to the recommended volume (#3: 60 ml, #4: 80 ml, and #5: 90 ml). After evaluation of the initial cuff pressure (CP), the CP was lowered in 10 cmH2O steps until a minimal cuff pressure of 30 cmH2O was achieved. The absence of an audible leak was required for a step-by-step reduction in the CP. Evacuated cuff volume, success rate, and airway injuries were documented. Data were expressed as medians (interquartile ranges [IQRs]). The comparison of CPs and cuff volumes was performed using the Mann-Whitney test. RESULTS: After initial inflation, the CP ranged from 105 cmH2O [90-120; #5] to 120 cmH2O [110-120; #3]. Lowering the CP to 60 cmH2O resulted in a reduced cuff volume ranging from 47 ml [44-54; #3] to 77 ml [75-82; #5] compared to the initial inflation (p < 0.001). Leakage occurred more frequently when the CP was lowered to 40 cmH2O compared to the initial inflation (44/54 [81%]; p < 0.01). Using a CP between 50 cmH2O and 60 cmH2O, a leakage rate of 3/54 (5%) was observed, compared to a rate of 11/54 (21%) when using a CP lower than 50 cmH2O. The overall success rate was 90%, and airway injury occurred in 7% of patients (4/60). CONCLUSION: We found significant overinflation of the revised LTS-D using the recommended volume for initial cuff inflation. A CP of 60 cmH2O was found to be sufficient for ventilation in the majority of patients evaluated. Checking and adjusting the CP in laryngeal tubes is mandatory to avoid overinflation. TRIAL REGISTRATION: ClinicalTrials.gov NCT02300337 . Registered: 20 November 2014.

Comparison of the gold standard of hemoglobin measurement with the clinical standard (BGA) and noninvasive hemoglobin measurement (SpHb) in small children: a prospective diagnostic observational study.

INTRODUCTION: Collecting a blood sample is usually necessary to measure hemoglobin levels in children. Especially in small children, noninvasively measuring the hemoglobin level could be extraordinarily helpful, but its precision and accuracy in the clinical environment remain unclear. In this study, noninvasive hemoglobin measurement and blood gas analysis were compared to hemoglobin measurement in a clinical laboratory. METHODS: In 60 healthy preoperative children (0.2-7.6 years old), hemoglobin was measured using a noninvasive method (SpHb; Radical-7 Pulse Co-Oximeter), a blood gas analyzer (clinical standard, BGAHb; ABL 800 Flex), and a laboratory hematology analyzer (reference method, labHb; Siemens Advia). Agreement between the results was assessed by Bland-Altman analysis and by determining the percentage of outliers. RESULTS: Sixty SpHb measurements, 60 labHb measurements, and 59 BGAHb measurements were evaluated. In 38% of the children, the location of the SpHb sensor had to be changed more than twice for the signal quality to be sufficient. The bias/limits of agreement between SpHb and labHb were -0.65/-3.4 to 2.1 g·dl(-1) . Forty-four percent of the SpHb values differed from the reference value by more than 1 g·dl(-1) . Age, difficulty of measurement, and the perfusion index (PI) had no influence on the accuracy of SpHb. The bias/limits of agreement between BGAHb and labHb were 1.14/-1.6 to 3.9 g·dl(-1) . Furthermore, 66% of the BGAHb values differed from the reference values by more than 1 g·dl(-1) . The absolute mean difference between SpHb and labHb (1.1 g·dl(-1) ) was smaller than the absolute mean difference between BGAHb and labHb (1.5 g·dl(-1) /P = 0.024). CONCLUSION: Noninvasive measurement of hemoglobin agrees more with the reference method than the measurement of hemoglobin using a blood gas analyzer. However, both methods can show clinically relevant differences from the reference method (ClinicalTrials.gov: NCT01693016).

The novel intubating laryngeal tube (iLTS-D) is comparable to the intubating laryngeal mask (Fastrach) - a prospective randomised manikin study.

BACKGROUND: Supraglottic devices are helpful for inexperienced providers who perform ventilation in emergency situations. Most supraglottic devices do not allow secondary tracheal intubation through the device. The novel intubating laryngeal tube (iLTS-D) and the intubating laryngeal mask (Fastrach) are devices that offer supraglottic ventilation and secondary tracheal intubation. METHODS: We evaluated the novel iLTS-D and compared it to the established Fastrach using a manikin-based study. Participants used both devices in a randomised order. The participants conducted four consecutive trials on a manikin. One trial was composed of the following procedures. First, participants ventilated the manikin using either iLTS-D or Fastrach. 'Time to ventilation', success rates and number of attempts were recorded for the supraglottic device. Second, participants intubated the manikin through the previously inserted supraglottic device. 'Time to tracheal ventilation', success rate and tube localisation were recorded. The primary endpoint was the results of the final fourth trial, which mirrored the standardised training of trials 1, 2 and 3. RESULTS: A total of 64 participants were enrolled. All of the participants successfully inserted both devices on their first attempt in trial 4. Fastrach was applied 1 s faster in trial 4 than the iLTS-D (median 'time to ventilation' Fastrach: 13.5 s., iLTS-D: 14.5 s., p = 0.04). All participants successfully intubated through both devices in trial 4. There was no difference in 'time to tracheal ventilation' by tracheal intubation between either device (median 'time to tracheal ventilation': Fastrach: 14.0 s., iLTS-D: 14.0 s., p = 0.16). CONCLUSION: The iLTS-D performed similarly to the ILMA in insertion and intubation times in a manikin setting.

Endotracheal intubation using the C-MAC® video laryngoscope or the Macintosh laryngoscope: a prospective, comparative study in the ICU.

INTRODUCTION: Endotracheal intubation in the ICU is a challenging procedure and is frequently associated with life-threatening complications. The aim of this study was to investigate the effect of the C-MAC® video laryngoscope on laryngeal view and intubation success compared with direct laryngoscopy. METHODS: In a single-center, prospective, comparative before-after study in an anesthetist-lead surgical ICU of a tertiary university hospital, predictors of potentially difficult tracheal intubation, number of intubation attempts, success rate and glottic view were evaluated during a 2-year study period (first year, Macintosh laryngoscopy (ML); second year, C-MAC®). RESULTS: A total of 274 critically ill patients requiring endotracheal intubation were included; 113 intubations using ML and 117 intubations using the C-MAC® were assessed. In patients with at least one predictor for difficult intubation, the C-MAC® resulted in more successful intubations on first attempt compared with ML (34/43, 79% vs. 21/38, 55%; P = 0.03). The visualization of the glottis with ML using Cormack and Lehane (C&L) grading was more frequently rated as difficult (20%, C&L grade 3 and 4) compared with the C-MAC® (7%, C&L grade 3 and 4) (P < 0.0001). CONCLUSION: Use of the C-MAC® video laryngoscope improved laryngeal imaging and improved the intubating success rate on the first attempt in patients with predictors for difficult intubation in the ICU setting. Video laryngoscopy seems to be a useful tool in the ICU where potentially difficult endotracheal intubations regularly occur.

Lay basic life support: the current situation in a medium-sized German town.

OBJECTIVE: Basic life support (BLS) by laypersons is essential for surviving sudden cardiac death in the community. The present study investigates BLS skill knowledge of German laypersons in a public community place and examines the effect of the interval between the last BLS course and present skills in cardiopulmonary resuscitation (CPR). METHODS: Participants were randomly recruited at a public place in a medium-sized German town. Volunteers were confronted with a fictitious cardiac arrest situation using a BLS training manikin and were asked to help. Using a standardised evaluation sheet, measures were documented. Participants' demographic data were evaluated after completion of the scenario. RESULTS: None of the participants (n=89; male=42, female=47) followed the current BLS algorithm correctly; independent from the last CPR course was attended. Most steps were performed in random order. 43% (n=38) of participants checked for responsiveness, 65% (n=58) performed chest compressions, and 63% (n=56) delivered rescue breathing. 10% (n=9) of participants were unable to name a national emergency telephone number. Laypersons who attended a BLS course more than 10 years ago showed a significant lack of BLS knowledge and failed more often to deliver chest compressions and rescue breathing. CONCLUSIONS: The present study demonstrates that current CPR guidelines for BLS are not followed by laypersons in a medium-sized town in Germany. These data suggest that CPR refresher courses as well as implication of BLS guidelines in daily life are warranted.

Estradiol after cardiac arrest and cardiopulmonary resuscitation is neuroprotective and mediated through estrogen receptor-beta.

We evaluated long-term administration of estrogen after cardiac arrest and cardiopulmonary resuscitation (CA/CPR) on neurohistopathological and behavioral outcome. We also examined the effect of estrogen receptor (ER) stimulation using ER-alpha agonist propyl pyrazole triol (PPT) and ER-beta agonist diarylpropionitrile (DPN) on neuronal survival after CA/CPR to determine whether possible neuroprotective effects of estrogen are ER-mediated. Male C57Bl/6 mice underwent 10 mins of CA/CPR and 3-day survival. In protocol 1, intravenous injection of vehicle (NaCl 0.9%) and 0.5 or 2.5 microg 17beta-estradiol (E2 loading dose) was performed followed by subcutaneous implants containing vehicle (oil) or E2 (12.6 microg), according to a treatment group. In experimental protocol 2, mice were injected (intravenously) with the ER-alpha agonist PPT or ER-beta agonist DPN followed by Alzet pump implants (subcutaneously) containing PPT (200 microg) or DPN (800 microg). Long-term E2 administration reduced neuronal injury in the striatum after administration of either loading dose (41%+/-19%, 35%+/-26% of injured neurons), as compared with vehicle (68%+/-7%, P<0.01), with no effect in the hippocampal CA1 field. In protocol 2, treatment with ER-beta agonist DPN reduced neuronal injury in the striatum (51%+/-13% injured neurons) as compared with ER-alpha agonist PPT (68%+/-10%) and vehicle (69%+/-11%; P<0.01). Estrogen receptor-beta agonist DPN reduced neuronal injury in the hippocampal CA1 field (29%+/-22% injured neurons) as compared with ER-alpha agonist PPT treatment (62%+/-33%; P<0.05). Injury was not different in hippocampal CA1 between vehicle and ER-alpha agonist-treated animals. We conclude that long-term E2 administration after CA/CPR is neuroprotective and that this effect is most likely mediated via ER-beta.

An early bolus of hypertonic saline hydroxyethyl starch improves long-term outcome after global cerebral ischemia.

OBJECTIVE: The beneficial effect of hypertonic saline solutions in the emergency treatment of shock and traumatic brain injury is well described. The present study determines effects of a single bolus of hypertonic saline on long-term survival, neurologic function, and neuronal survival 10 days after global cerebral ischemia. In addition, we evaluated the therapeutic window for hypertonic saline treatment (early vs. delayed application). DESIGN: Laboratory experiment. SETTING: University laboratory. SUBJECTS: Male Wistar rats weighing 240-330 g. INTERVENTIONS: Rats were submitted to temporal global cerebral ischemia using temporary bilateral carotid occlusion combined with hypobaric hypotension. Animals received 7.5% saline/6% hydroxyethyl starch (HHS) or vehicle (NaCl 0.9%) at either 1.5 mins (early treatment) or 31.5 mins (delayed treatment) of reperfusion. Regional cerebral blood flow (rCBF) and physiologic variables were measured during insult and early reperfusion. Animal survival and neurologic function were evaluated throughout the 10-day observation period. Quantification of brain injury was performed on day 10. MEASUREMENTS AND MAIN RESULTS: Early treatment with HHS resulted in a robust restoration of rCBF after ischemia, reduced postischemic mortality by 77% (9% vs. 39% in vehicle-treated controls), ameliorated neurologic performance (Neuro-Deficit-Score 10 days after insult, 96 +/- 0.7 vs. 85 +/- 1.4, mean +/- se), and almost blunted neuronal cell death (hippocampal CA1, 2150 +/- 191 vs. 884 +/- 141 neurons/mm; cortex, 1746 +/- 91 vs. 1060 +/- 112). In contrast, delayed treatment resulted in no sustained effects. CONCLUSIONS: Timing of HHS treatment is critical after experimental global cerebral ischemia to reduce mortality, improve neurologic function, and neuronal survival. Our results suggest that early application of HHS may be a potential neuroprotective strategy after global cerebral ischemia.

Dose-dependent neuroprotection by 17beta-estradiol after cardiac arrest and cardiopulmonary resuscitation.

OBJECTIVE: Despite recent advances in the treatment of cardiac arrest, neurologic outcome remains poor. 17beta-Estradiol (E2) has been widely shown to reduce damage after experimental brain injury. The present study determined whether E2 also improves neuronal survival after experimental cardiac arrest and cardiopulmonary resuscitation and if any protection is dose-dependent. DESIGN: A randomized trial. SETTING: A research laboratory. SUBJECTS: Male C57Bl/6 mice weighing 20-25 g. INTERVENTIONS: Mice were randomized into one of six groups, receiving treatment with 0.5, 2.5, 12.5, 25, or 50 mug of E2 or vehicle 1.5 mins after return of spontaneous circulation. Ten minutes after induction of cardiac arrest (by KCl injection), cardiopulmonary resuscitation was initiated (with chest compressions, intravenous epinephrine, and ventilation with 100% O2). Additional animals of each E2-treated group were used for plasma estradiol-level analysis. Brains were removed for quantification of injury in the hippocampus and caudoputamen on day 3. MEASUREMENTS AND MAIN RESULTS: The E2 0.5 group had physiologic estrogen levels 60 min after injection (mean +/- se, 28 +/- 5 pg/mL), whereas the E2 50 group still showed supraphysiologic levels 360 min after administration (245 +/- 32 pg/mL). Hippocampal damage was not altered with E2 treatment. Only posttreatment with the lowest E2 dose (E2 0.5) resulted in attenuated neuronal injury in the rostral and caudal caudoputamen (34 +/- 11% and 27 +/- 11%), in comparison with vehicle (68 +/- 5, p < .05; 63 +/- 4%, p < .001). Higher E2 doses did not affect brain injury. CONCLUSIONS: We conclude that E2 has a critical dosing effect on neuronal survival, physiologic levels of E2 are neuroprotective after cardiac arrest/cardiopulmonary resuscitation, and acute exposure is sufficient for brain resuscitation.