Online Letters to the Editor
The authors reply:
W
e thank Esquinas and Soo Hoo (1) for their interest in our study (2). On the one hand, it is true that our definition of low-, medium-, and high-volume units is somehow arbitrary but, on the other hand, it still has some objective numerical background since it relies on the distribution of case volume in the whole group of centers, as described using tertiles. We find it difficult to imagine a less arbitrary approach since, as outlined by Esquinas and Soo Hoo (1), “There are no existing validated criterion that properly defines ICU volume and accounts for experience and expertise.” Indeed, similar criteria were used in other recent studies demonstrating relationships between case volume and outcomes in various fields (3–5). Recognizing that our choice was somehow arbitrary, we performed sensitivity analyses, showing that using quartiles instead of tertiles did not change the findings. These considerations should not blunt what we believe is the most important message, that is, that practice allows to improve. Complex prospective qualitative studies would be required to appropriately evaluate the corresponding learning effect. Awaiting for additional data on this aspect of the question, we do not share the pessimistic view that our results imply that low-volume ICUs will never attain excellence: they might just need to develop different learning strategies and organizations, and we hope that our results will help raising awareness on this point. Another solution could be to group small units, which is a trend in several healthcare systems at present. But such an approach has much wider implications than can be discussed here in terms of health politics. It is certainly true that it would have been of interest to better characterize the ICUs based on their bed capacity, nurse ratio, and medical staff characteristics. But integrating these criteria would be highly problematic since it would require to reconstitute the complete history of all studied units during the whole study period. Furthermore, even if some of our findings were related to an influence of these ICU characteristics, it would not compromise our conclusion, that is, “that clinician and staff experience and/or specific processes of care common to high-volume centers may be associated with outcomes” in this area. Indeed, we fully agree with Esquinas and Soo Hoo (1) when they raise the challenging question of factors contributing to successful management of acute exacerbations of chronic obstructive pulmonary disease (AECOPD) by noninvasive ventilation (NIV). Regarding severity of illness, it must be outlined that it was indeed assessed not only by pH but also by Simplified Acute Physiology Score 2 score. It would certainly have been interesting to record an AECOPD-specific severity score, but none was available. Knowledge of the severity of chronic obstructive pulmonary disease at stable state (level of lung function, history of exacerbations, prognostic indices such as the B [Body mass index], O [airflow Obstruction], D [Dyspnea], and E [Exercice capacity] score) would also be of value but is, unfortunately, relatively infrequently available in ICU patients. Regarding the use of NIV according to the categories of ICU, Table 3 in (2) indeed confirms that our hypothesis that high volume is associated with the highest use of NIV.
e250
www.ccmjournal.org
The authors have disclosed that they do not have any potential conflicts of interest. Martin Dres, MD, Service de Pneumologie et Réanimation Médicale, Hôpital Hôtel Dieu, Assistance Publique Hôpitaux de Paris, University Paris Descartes, Paris, France; Thi-Chien Tran MSc, Philippe Aegerter, MD, PhD, Département de Santé Publique, Hôpital Ambroise Paré, AP-HP, Boulogne, France; and UPRES EA2506, University Versailles-Saint Quentin, Paris, France; Antoine Rabbat, MD, Service de Pneumologie et Réanimation Médicale, Hôpital Hôtel Dieu, Assistance Publique Hôpitaux de Paris, University Paris Descartes, Paris, France; Bertrand Guidet, MD, Service de Réanimation Médicale, Hôpital Saint Antoine, Assistance Publique Hôpitaux de Paris, University Pierre et Marie Curie, Paris, France, and U707, Institut National de la Santé et de la Recherche Médicale, Paris, France; Gerard Huchon, MD, PhD, Service de Pneumologie et Réanimation Médicale, Hôpital Hôtel Dieu, Assistance Publique Hôpitaux de Paris, University Paris Descartes, Paris, France; Nicolas Roche, MD, PhD, Service de Pneumologie et Réanimation Médicale, Hôpital Hôtel Dieu, Assistance Publique Hôpitaux de Paris, University Paris Descartes, Paris, France; on behalf of the CUB-REA Group
REFERENCES
1. Esquinas AM, Soo Hoo GW: Efficacy of Noninvasive Ventilation and Hospital Outcomes of Acute Chronic Obstructive Pulmonary Disease in the ICU: A Question of Volume Alone? Crit Care Med 2014; 42:e249 2. Dres M, Tran T-C, Aegerter P, et al: Influence of ICU case-volume on the management and hospital outcomes of acute exacerbations of chronic obstructive pulmonary disease. Crit Care Med 2013; 41:1884–1892 3. Zuber B, Tran TC, Aegerter P, et al; CUB-Réa Network: Impact of case volume on survival of septic shock in patients with malignancies. Crit Care Med 2012; 40:55–62 4. Kahn JM, Goss CH, Heagerty PJ, et al: Hospital volume and the outcomes of mechanical ventilation. N Engl J Med 2006; 355:41–50 5. Lecuyer L, Chevret S, Guidet B, et al: Case volume and mortality in haematological patients with acute respiratory failure. Eur Respir J 2008; 32:748–754 DOI: 10.1097/CCM.0000000000000153
Severe Cerebral Arterial Gas Embolism Can Be Fatal; What About Cerebral Venous Gas Embolism?
W
eenink et al (1) need to be commended for their ongoing attempts to unravel the effects of cerebral gas embolism on the brain and lately the response of the swine brain, injured by air embolism to hyperbaric oxygen (HBO) therapy. Cerebral gas embolism is such a devastating disease, and although very uncommon, it is an important and underdiagnosed issue in healthcare. Not only is this often a devastating or fatal complication for the patient, but in the case of iatrogenic causes, it may also have career changing or even career ending effects on clinicians. It has been classified as a “NEVER EVENT” both in the United States and in the United Kingdom, which means it is preventable to a large extent. March 2014 • Volume 42 • Number 3
Online Letters to the Editor
Weenink et al (2) have looked for the ideal animal model, which is always a difficult task. One might think that a primate model might be closer to that of the human, particularly when testing brain function. The different cerebral vascular anatomy in the pig obviously has certain implications which may not always be evident. Their methodology appears sound, but inflicts very serious ischemia to the swine brain. By the way they injected air directly and repeatedly into the ascending pharyngeal artery (the equivalent of the internal carotid artery); the cerebral arterial circulation is directly exposed to the total bubble load. This is not the case in most instances of cerebral arterial gas embolism in humans where gas entering the systemic arterial circulation is distributed to the brain, the heart, and even the mesenteric and limb vessels. The prolonged exposure to bubbles in the swine model is an extremely harsh insult and certainly worse than most of the clinical events that are survivable and potentially reach a Hyperbaric Therapy Unit. The poor outcome in this swine model is not surprising. One might have expected repeated hyperbaric treatments in the human patient with a severe injury like this. In their experiment, they stopped at one treatment. This may or may not make a difference in their experimental model as the injury is so severe that nothing may change the outcome. One aspect of cerebral gas embolism that has not been addressed in their experimental work or in the accompanying editorial (3) is the significance of retrograde cerebral venous gas embolism. This is a subset of cerebral gas embolism, which is now better understood but hardly ever recognized in clinical cases. It has featured prominently in forensic medicine journals which indicate that patients do die of it (4). We would like to encourage the team to look at cerebral venous gas embolism in their animal model as well. More importantly, cases with cerebral venous gas embolism should be reported with enough detail to learn about the pathogenesis, management, and outcome from each new case with and without HBO therapy (5). Dr. Bothma is employed as the part-time Medical Director of Hyperbaric Unit and received support for travel form London Hyperbaric Unit (cost of travel and expenses paid for attending meetings for Continuing Medical Education purposes). Dr. Rice is employed as the Deputy Medical Director of London Hyperbaric Medicine and received support for travel from London Hyperbaric Medicine (cost of travel and attending courses for CME purposes is paid). Pieter A. Bothma, MB ChB, MMed, FCA(SA), Department of Anesthetics, James Paget University Hospital, Gorleston, Norfolk, United Kingdom; London Hyperbaric Unit, Whipps Cross University Hospital, Leytonstone, London, United Kingdom, and East of England Hyperbaric Unit, James Paget Hospital, Gorleston, Norfolk, United Kingdom; Neil E. Rice, MB ChB, MRCA, Department of Anesthetics, Whipps Cross University Hospital, Leytonstone, London, United Kingdom, and London Hyperbaric Unit, Whipps Cross University Hospital, Leytonstone, London, United Kingdom
Critical Care Medicine
REFERENCES
1. Weenink RP, Hollmann MW, Vrijdag XC, et al: Hyperbaric Oxygen Does Not Improve Cerebral Function When Started 2 or 4 Hours After Cerebral Arterial Gas Embolism in Swine. Crit Care Med 2013; 41:1719–1727 2. Weenink RP, Hollmann MW, van Hulst RA: Animal models of cerebral arterial gas embolism. J Neurosci Methods 2012; 205:233–245 3. Souday V, Radermacher P, Asfar P: Cerebral arterial gas embolism—A race against time! Crit Care Med 2013; 41:1817–1819 4. Schlimp CJ, Loimer T, Rieger M, et al: The potential of venous air embolism ascending retrograde to the brain. J Forensic Sci 2005; 50:906–909 5. Bothma PA, Brodbeck AE, Smith BA: Cerebral venous air embolism treated with hyperbaric oxygen: A case report. Diving Hyperb Med 2012; 42:101–103 DOI: 10.1097/CCM.0000000000000086
The authors reply:
W
e thank Bothma and Rice (1) for their interest in our research and the useful comments and suggestions from their part. Choosing the most appropriate animal model is indeed never an easy task. Despite its cerebrovascular disadvantages, especially the presence of the carotid rete, the swine presents some interesting upsides when compared with smaller animal models. Cardiovascular comparability to humans and a brain size that accommodates the use of multiple invasive monitoring techniques were the most important reasons for choosing this animal. Nevertheless, we may consider “scaling down” to smaller animals models (e.g., the rabbit) in the future, because of its more favorable cerebrovascular anatomy and its frequent use in cerebral arterial gas embolism research. Although primates may offer the closest approximation of the human situation, use of these animals is fraught with ethical and other limitations. As Bothma and Rice (1) mention, in clinical patients, the total bubble load is virtually never distributed solely to the brain. The goal of our model, however, was to inflict as homogeneous a damage as possible, and therefore, we chose to inject the air close to the cerebral circulation. Injection at a more proximal location would undoubtedly have resulted in a wider distribution of the air and therefore to less standardized damage to the brain. We agree with Bothma and Rice (1) that our model inflicts a large amount of damage. This may indeed be the reason that our single session of hyperbaric oxygen therapy was not successful and that even repeat sessions might not have been able to ameliorate the injury. One of the current goals of our research project is to continue the search for more refined methods of air embolization, to induce more standardized amounts of damage while increasing the comparability with the human situation. This task is complicated by the fact that the presentation (and therefore amount of air involved?) in clinical patients is also very heterogeneous. As for the suggestion by Bothma and Rice (1) to include investigation of retrograde cerebral venous gas embolism in our model, we find this a very interesting suggestion. The mechanisms involved in this type of air embolism share many similarities but also have important differences with cerebral arterial gas embolism. Given the fact that inducing retrograde www.ccmjournal.org
e251
The authors reply:
W
e thank Esquinas and Soo Hoo (1) for their interest in our study (2). On the one hand, it is true that our definition of low-, medium-, and high-volume units is somehow arbitrary but, on the other hand, it still has some objective numerical background since it relies on the distribution of case volume in the whole group of centers, as described using tertiles. We find it difficult to imagine a less arbitrary approach since, as outlined by Esquinas and Soo Hoo (1), “There are no existing validated criterion that properly defines ICU volume and accounts for experience and expertise.” Indeed, similar criteria were used in other recent studies demonstrating relationships between case volume and outcomes in various fields (3–5). Recognizing that our choice was somehow arbitrary, we performed sensitivity analyses, showing that using quartiles instead of tertiles did not change the findings. These considerations should not blunt what we believe is the most important message, that is, that practice allows to improve. Complex prospective qualitative studies would be required to appropriately evaluate the corresponding learning effect. Awaiting for additional data on this aspect of the question, we do not share the pessimistic view that our results imply that low-volume ICUs will never attain excellence: they might just need to develop different learning strategies and organizations, and we hope that our results will help raising awareness on this point. Another solution could be to group small units, which is a trend in several healthcare systems at present. But such an approach has much wider implications than can be discussed here in terms of health politics. It is certainly true that it would have been of interest to better characterize the ICUs based on their bed capacity, nurse ratio, and medical staff characteristics. But integrating these criteria would be highly problematic since it would require to reconstitute the complete history of all studied units during the whole study period. Furthermore, even if some of our findings were related to an influence of these ICU characteristics, it would not compromise our conclusion, that is, “that clinician and staff experience and/or specific processes of care common to high-volume centers may be associated with outcomes” in this area. Indeed, we fully agree with Esquinas and Soo Hoo (1) when they raise the challenging question of factors contributing to successful management of acute exacerbations of chronic obstructive pulmonary disease (AECOPD) by noninvasive ventilation (NIV). Regarding severity of illness, it must be outlined that it was indeed assessed not only by pH but also by Simplified Acute Physiology Score 2 score. It would certainly have been interesting to record an AECOPD-specific severity score, but none was available. Knowledge of the severity of chronic obstructive pulmonary disease at stable state (level of lung function, history of exacerbations, prognostic indices such as the B [Body mass index], O [airflow Obstruction], D [Dyspnea], and E [Exercice capacity] score) would also be of value but is, unfortunately, relatively infrequently available in ICU patients. Regarding the use of NIV according to the categories of ICU, Table 3 in (2) indeed confirms that our hypothesis that high volume is associated with the highest use of NIV.
e250
www.ccmjournal.org
The authors have disclosed that they do not have any potential conflicts of interest. Martin Dres, MD, Service de Pneumologie et Réanimation Médicale, Hôpital Hôtel Dieu, Assistance Publique Hôpitaux de Paris, University Paris Descartes, Paris, France; Thi-Chien Tran MSc, Philippe Aegerter, MD, PhD, Département de Santé Publique, Hôpital Ambroise Paré, AP-HP, Boulogne, France; and UPRES EA2506, University Versailles-Saint Quentin, Paris, France; Antoine Rabbat, MD, Service de Pneumologie et Réanimation Médicale, Hôpital Hôtel Dieu, Assistance Publique Hôpitaux de Paris, University Paris Descartes, Paris, France; Bertrand Guidet, MD, Service de Réanimation Médicale, Hôpital Saint Antoine, Assistance Publique Hôpitaux de Paris, University Pierre et Marie Curie, Paris, France, and U707, Institut National de la Santé et de la Recherche Médicale, Paris, France; Gerard Huchon, MD, PhD, Service de Pneumologie et Réanimation Médicale, Hôpital Hôtel Dieu, Assistance Publique Hôpitaux de Paris, University Paris Descartes, Paris, France; Nicolas Roche, MD, PhD, Service de Pneumologie et Réanimation Médicale, Hôpital Hôtel Dieu, Assistance Publique Hôpitaux de Paris, University Paris Descartes, Paris, France; on behalf of the CUB-REA Group
REFERENCES
1. Esquinas AM, Soo Hoo GW: Efficacy of Noninvasive Ventilation and Hospital Outcomes of Acute Chronic Obstructive Pulmonary Disease in the ICU: A Question of Volume Alone? Crit Care Med 2014; 42:e249 2. Dres M, Tran T-C, Aegerter P, et al: Influence of ICU case-volume on the management and hospital outcomes of acute exacerbations of chronic obstructive pulmonary disease. Crit Care Med 2013; 41:1884–1892 3. Zuber B, Tran TC, Aegerter P, et al; CUB-Réa Network: Impact of case volume on survival of septic shock in patients with malignancies. Crit Care Med 2012; 40:55–62 4. Kahn JM, Goss CH, Heagerty PJ, et al: Hospital volume and the outcomes of mechanical ventilation. N Engl J Med 2006; 355:41–50 5. Lecuyer L, Chevret S, Guidet B, et al: Case volume and mortality in haematological patients with acute respiratory failure. Eur Respir J 2008; 32:748–754 DOI: 10.1097/CCM.0000000000000153
Severe Cerebral Arterial Gas Embolism Can Be Fatal; What About Cerebral Venous Gas Embolism?
W
eenink et al (1) need to be commended for their ongoing attempts to unravel the effects of cerebral gas embolism on the brain and lately the response of the swine brain, injured by air embolism to hyperbaric oxygen (HBO) therapy. Cerebral gas embolism is such a devastating disease, and although very uncommon, it is an important and underdiagnosed issue in healthcare. Not only is this often a devastating or fatal complication for the patient, but in the case of iatrogenic causes, it may also have career changing or even career ending effects on clinicians. It has been classified as a “NEVER EVENT” both in the United States and in the United Kingdom, which means it is preventable to a large extent. March 2014 • Volume 42 • Number 3
Online Letters to the Editor
Weenink et al (2) have looked for the ideal animal model, which is always a difficult task. One might think that a primate model might be closer to that of the human, particularly when testing brain function. The different cerebral vascular anatomy in the pig obviously has certain implications which may not always be evident. Their methodology appears sound, but inflicts very serious ischemia to the swine brain. By the way they injected air directly and repeatedly into the ascending pharyngeal artery (the equivalent of the internal carotid artery); the cerebral arterial circulation is directly exposed to the total bubble load. This is not the case in most instances of cerebral arterial gas embolism in humans where gas entering the systemic arterial circulation is distributed to the brain, the heart, and even the mesenteric and limb vessels. The prolonged exposure to bubbles in the swine model is an extremely harsh insult and certainly worse than most of the clinical events that are survivable and potentially reach a Hyperbaric Therapy Unit. The poor outcome in this swine model is not surprising. One might have expected repeated hyperbaric treatments in the human patient with a severe injury like this. In their experiment, they stopped at one treatment. This may or may not make a difference in their experimental model as the injury is so severe that nothing may change the outcome. One aspect of cerebral gas embolism that has not been addressed in their experimental work or in the accompanying editorial (3) is the significance of retrograde cerebral venous gas embolism. This is a subset of cerebral gas embolism, which is now better understood but hardly ever recognized in clinical cases. It has featured prominently in forensic medicine journals which indicate that patients do die of it (4). We would like to encourage the team to look at cerebral venous gas embolism in their animal model as well. More importantly, cases with cerebral venous gas embolism should be reported with enough detail to learn about the pathogenesis, management, and outcome from each new case with and without HBO therapy (5). Dr. Bothma is employed as the part-time Medical Director of Hyperbaric Unit and received support for travel form London Hyperbaric Unit (cost of travel and expenses paid for attending meetings for Continuing Medical Education purposes). Dr. Rice is employed as the Deputy Medical Director of London Hyperbaric Medicine and received support for travel from London Hyperbaric Medicine (cost of travel and attending courses for CME purposes is paid). Pieter A. Bothma, MB ChB, MMed, FCA(SA), Department of Anesthetics, James Paget University Hospital, Gorleston, Norfolk, United Kingdom; London Hyperbaric Unit, Whipps Cross University Hospital, Leytonstone, London, United Kingdom, and East of England Hyperbaric Unit, James Paget Hospital, Gorleston, Norfolk, United Kingdom; Neil E. Rice, MB ChB, MRCA, Department of Anesthetics, Whipps Cross University Hospital, Leytonstone, London, United Kingdom, and London Hyperbaric Unit, Whipps Cross University Hospital, Leytonstone, London, United Kingdom
Critical Care Medicine
REFERENCES
1. Weenink RP, Hollmann MW, Vrijdag XC, et al: Hyperbaric Oxygen Does Not Improve Cerebral Function When Started 2 or 4 Hours After Cerebral Arterial Gas Embolism in Swine. Crit Care Med 2013; 41:1719–1727 2. Weenink RP, Hollmann MW, van Hulst RA: Animal models of cerebral arterial gas embolism. J Neurosci Methods 2012; 205:233–245 3. Souday V, Radermacher P, Asfar P: Cerebral arterial gas embolism—A race against time! Crit Care Med 2013; 41:1817–1819 4. Schlimp CJ, Loimer T, Rieger M, et al: The potential of venous air embolism ascending retrograde to the brain. J Forensic Sci 2005; 50:906–909 5. Bothma PA, Brodbeck AE, Smith BA: Cerebral venous air embolism treated with hyperbaric oxygen: A case report. Diving Hyperb Med 2012; 42:101–103 DOI: 10.1097/CCM.0000000000000086
The authors reply:
W
e thank Bothma and Rice (1) for their interest in our research and the useful comments and suggestions from their part. Choosing the most appropriate animal model is indeed never an easy task. Despite its cerebrovascular disadvantages, especially the presence of the carotid rete, the swine presents some interesting upsides when compared with smaller animal models. Cardiovascular comparability to humans and a brain size that accommodates the use of multiple invasive monitoring techniques were the most important reasons for choosing this animal. Nevertheless, we may consider “scaling down” to smaller animals models (e.g., the rabbit) in the future, because of its more favorable cerebrovascular anatomy and its frequent use in cerebral arterial gas embolism research. Although primates may offer the closest approximation of the human situation, use of these animals is fraught with ethical and other limitations. As Bothma and Rice (1) mention, in clinical patients, the total bubble load is virtually never distributed solely to the brain. The goal of our model, however, was to inflict as homogeneous a damage as possible, and therefore, we chose to inject the air close to the cerebral circulation. Injection at a more proximal location would undoubtedly have resulted in a wider distribution of the air and therefore to less standardized damage to the brain. We agree with Bothma and Rice (1) that our model inflicts a large amount of damage. This may indeed be the reason that our single session of hyperbaric oxygen therapy was not successful and that even repeat sessions might not have been able to ameliorate the injury. One of the current goals of our research project is to continue the search for more refined methods of air embolization, to induce more standardized amounts of damage while increasing the comparability with the human situation. This task is complicated by the fact that the presentation (and therefore amount of air involved?) in clinical patients is also very heterogeneous. As for the suggestion by Bothma and Rice (1) to include investigation of retrograde cerebral venous gas embolism in our model, we find this a very interesting suggestion. The mechanisms involved in this type of air embolism share many similarities but also have important differences with cerebral arterial gas embolism. Given the fact that inducing retrograde www.ccmjournal.org
e251
