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Cerebral resuscitation: Shifting away from the basics
Accepted Manuscript Title: Cerebral Resuscitation: Shifting Away From the Basics Author: Rory J. Spiegel PII: DOI: Reference:
S0300-9572(17)30639-1 https://doi.org/10.1016/j.resuscitation.2017.09.028 RESUS 7331
To appear in:
Resuscitation
Author: Michael Winters PII: DOI: Reference:
S0300-9572(17)30639-1 https://doi.org/10.1016/j.resuscitation.2017.09.028 RESUS 7331
To appear in:
Resuscitation
Author: Michael T. McCurdy PII: DOI: Reference:
S0300-9572(17)30639-1 https://doi.org/10.1016/j.resuscitation.2017.09.028 RESUS 7331
To appear in:
Resuscitation
Received date: Accepted date:
23-9-2017 25-9-2017
Please cite this article as: McCurdy Michael T.Cerebral Resuscitation: Shifting Away From the Basics.Resuscitation https://doi.org/10.1016/j.resuscitation.2017.09.028 This is a PDF file of an unedited manuscript that has been accepted for publication. As a service to our customers we are providing this early version of the manuscript. The manuscript will undergo copyediting, typesetting, and review of the resulting proof before it is published in its final form. Please note that during the production process errors may be discovered which could affect the content, and all legal disclaimers that apply to the journal pertain.
Cerebral Resuscitation: Shifting Away From the Basics Rory J Spiegel, MD Critical Care Fellow in the Department of Pulmonary Critical Care University of Maryland Medical Center Email: [email protected] Michael Winters, MD, FACEP, FAAEM Associate Professor of Emergency Medicine and Medicine University of Maryland School of Medicine Baltimore, Maryland Michael T. McCurdy, MD Associate Professor, Pulmonary & Critical Care Medicine Associate Professor, Emergency Medicine University of Maryland School of Medicine Email: [email protected]
We read with interest the article by Wang et al titled “Post-resuscitation arterial oxygen and carbon dioxide and outcomes after out-of-hospital cardiac arrest.” We congratulate the authors on their rigorous analysis of the ROC Epistry that highlights the prognostic value of oxygen (O2) and carbon dioxide (CO2) tension in patients presenting to the emergency department (ED) following out-of-hospital cardiac arrest (OHCA) (1). Though the authors report that hypercapnia, hypocapnia, and hypoxia were associated with increased mortality during the first 24 hours following cardiac arrest, we urge caution in the interpretation of these findings. Despite the complex statistical methodology of the authors’ analysis, the causative nature of these findings is impossible to determine without randomization. As such, the results should not be used to justify strategies that encourage normal O2 and CO2 tensions in the post-arrest patient. In contrast to normocapnia, mild hypercapnia increases cerebral blood flow and regional cerebral tissue O2 saturation in post-arrest patients ventilated using a mild hypercapneic strategy (2). A pilot study by Eastwood and colleagues found that post-arrest patients randomized to a hypercapneic strategy trended toward improved mortality and functional neurological outcomes (3). These beneficial effects may not be due to CO2 tension directly, but rather to a hypercapnia-induced mild acidemia. Although the pH values (mean 7.16) were provided for the first post-arrest ABG, no further pH levels were reported despite a median of three ABGs per patient during the first 24 hours of hospitalization. The prevalence of alkalemia at any point during the first 24h hours is
unknown. Alkalemia, independent of CO2 tension, decreases cerebral blood flow. (4) Notwithstanding, our concern extends beyond cerebral blood flow alone. While a neutral pH may optimize hemoglobin saturation in the lungs, it may discourage O2 unloading at tissues where a more acidotic state is preferred (5). Given our understanding of oxyhemoglobin dissociation, we question whether a forced respiratory alkalosis may shift the curve to the left and produce local end-organ tissue hypoxia despite both adequate cerebral perfusion and adequate blood oxygenation. Importantly, the prognostic capabilities of O2 and CO2 tension in the post-arrest patient may simply represent physiologic stress induced by the etiology of the arrest. We contend that, in times of stress, an acidotic environment encourages increased cerebral blood flow and facilitates a rightward shift of the oxyhemoglobin dissociation to unload O2 at the tissues. As such, resuscitative efforts should transition from forced physiologic normality to strategies intent on optimizing neurologic recovery. We must look beyond macrocirculatory and microcirculatory optimization to address the additional determinants and impact of O2 unloading at those vulnerable tissues we try so hard to protect. Reference Sources Cited: 1. Wang HE, Prince DK, Drennan IR, et al. Post-resuscitation arterial oxygen and carbon dioxide and outcomes after out-of-hospital cardiac arrest. Resuscitation. 2017. 2. Eastwood GM, Tanaka A, Bellomo R. Cerebral oxygenation in mechanically ventilated early cardiac arrest survivors: The impact of hypercapnia. Resuscitation. 2016; 102:11-6. 3. Eastwood GM, Schneider AG, Suzuki S, et al. Targeted therapeutic mild hypercapnia after cardiac arrest: A phase II multi-centre randomised controlled trial (the CCC trial). Resuscitation. 2016; 104:83-90. 4. Yoon S, Zuccarello M, Rapoport RM. pCO(2) and pH regulation of cerebral blood flow. Front Physiol. 2012; 3:365. 5. Dash RK, Korman B, Bassingthwaighte JB. Simple accurate mathematical models of blood HbO2 and HbCO2 dissociation curves at varied physiological conditions: evaluation and comparison with other models. Eur J Appl Physiol. 2016. 116:97-113.
S0300-9572(17)30639-1 https://doi.org/10.1016/j.resuscitation.2017.09.028 RESUS 7331
To appear in:
Resuscitation
Author: Michael Winters PII: DOI: Reference:
S0300-9572(17)30639-1 https://doi.org/10.1016/j.resuscitation.2017.09.028 RESUS 7331
To appear in:
Resuscitation
Author: Michael T. McCurdy PII: DOI: Reference:
S0300-9572(17)30639-1 https://doi.org/10.1016/j.resuscitation.2017.09.028 RESUS 7331
To appear in:
Resuscitation
Received date: Accepted date:
23-9-2017 25-9-2017
Please cite this article as: McCurdy Michael T.Cerebral Resuscitation: Shifting Away From the Basics.Resuscitation https://doi.org/10.1016/j.resuscitation.2017.09.028 This is a PDF file of an unedited manuscript that has been accepted for publication. As a service to our customers we are providing this early version of the manuscript. The manuscript will undergo copyediting, typesetting, and review of the resulting proof before it is published in its final form. Please note that during the production process errors may be discovered which could affect the content, and all legal disclaimers that apply to the journal pertain.
Cerebral Resuscitation: Shifting Away From the Basics Rory J Spiegel, MD Critical Care Fellow in the Department of Pulmonary Critical Care University of Maryland Medical Center Email: [email protected] Michael Winters, MD, FACEP, FAAEM Associate Professor of Emergency Medicine and Medicine University of Maryland School of Medicine Baltimore, Maryland Michael T. McCurdy, MD Associate Professor, Pulmonary & Critical Care Medicine Associate Professor, Emergency Medicine University of Maryland School of Medicine Email: [email protected]
We read with interest the article by Wang et al titled “Post-resuscitation arterial oxygen and carbon dioxide and outcomes after out-of-hospital cardiac arrest.” We congratulate the authors on their rigorous analysis of the ROC Epistry that highlights the prognostic value of oxygen (O2) and carbon dioxide (CO2) tension in patients presenting to the emergency department (ED) following out-of-hospital cardiac arrest (OHCA) (1). Though the authors report that hypercapnia, hypocapnia, and hypoxia were associated with increased mortality during the first 24 hours following cardiac arrest, we urge caution in the interpretation of these findings. Despite the complex statistical methodology of the authors’ analysis, the causative nature of these findings is impossible to determine without randomization. As such, the results should not be used to justify strategies that encourage normal O2 and CO2 tensions in the post-arrest patient. In contrast to normocapnia, mild hypercapnia increases cerebral blood flow and regional cerebral tissue O2 saturation in post-arrest patients ventilated using a mild hypercapneic strategy (2). A pilot study by Eastwood and colleagues found that post-arrest patients randomized to a hypercapneic strategy trended toward improved mortality and functional neurological outcomes (3). These beneficial effects may not be due to CO2 tension directly, but rather to a hypercapnia-induced mild acidemia. Although the pH values (mean 7.16) were provided for the first post-arrest ABG, no further pH levels were reported despite a median of three ABGs per patient during the first 24 hours of hospitalization. The prevalence of alkalemia at any point during the first 24h hours is
unknown. Alkalemia, independent of CO2 tension, decreases cerebral blood flow. (4) Notwithstanding, our concern extends beyond cerebral blood flow alone. While a neutral pH may optimize hemoglobin saturation in the lungs, it may discourage O2 unloading at tissues where a more acidotic state is preferred (5). Given our understanding of oxyhemoglobin dissociation, we question whether a forced respiratory alkalosis may shift the curve to the left and produce local end-organ tissue hypoxia despite both adequate cerebral perfusion and adequate blood oxygenation. Importantly, the prognostic capabilities of O2 and CO2 tension in the post-arrest patient may simply represent physiologic stress induced by the etiology of the arrest. We contend that, in times of stress, an acidotic environment encourages increased cerebral blood flow and facilitates a rightward shift of the oxyhemoglobin dissociation to unload O2 at the tissues. As such, resuscitative efforts should transition from forced physiologic normality to strategies intent on optimizing neurologic recovery. We must look beyond macrocirculatory and microcirculatory optimization to address the additional determinants and impact of O2 unloading at those vulnerable tissues we try so hard to protect. Reference Sources Cited: 1. Wang HE, Prince DK, Drennan IR, et al. Post-resuscitation arterial oxygen and carbon dioxide and outcomes after out-of-hospital cardiac arrest. Resuscitation. 2017. 2. Eastwood GM, Tanaka A, Bellomo R. Cerebral oxygenation in mechanically ventilated early cardiac arrest survivors: The impact of hypercapnia. Resuscitation. 2016; 102:11-6. 3. Eastwood GM, Schneider AG, Suzuki S, et al. Targeted therapeutic mild hypercapnia after cardiac arrest: A phase II multi-centre randomised controlled trial (the CCC trial). Resuscitation. 2016; 104:83-90. 4. Yoon S, Zuccarello M, Rapoport RM. pCO(2) and pH regulation of cerebral blood flow. Front Physiol. 2012; 3:365. 5. Dash RK, Korman B, Bassingthwaighte JB. Simple accurate mathematical models of blood HbO2 and HbCO2 dissociation curves at varied physiological conditions: evaluation and comparison with other models. Eur J Appl Physiol. 2016. 116:97-113.