Editorials
Critical Care Management of Two Patients With Ebola: A Biocontainment Unit Demystified* Parizad Torabi-Parizi, MD Critical Care Medicine Department, Clinical Center National Institutes of Health Bethesda, MD
I
n less than 1 year, during the dramatic rise of Ebola virus disease in Western Africa, the medical community has been required to respond to multiple areas of uncertainty regarding the best treatments for patients and the safety of healthcare workers. For patients repatriated to their home countries in Europe and the United States, the opportunity to provide higher levels of care added a new layer of complexity regarding the safety and appropriateness of invasive procedures (1–3). Several groups have issued practice guidelines for the safe provision of care to patients infected with the Ebola virus (4–6). Detailed reports of the process of delivering intensive care to these patients in resource-rich settings, however, are limited. In this issue of Critical Care Medicine, Johnson et al (7) provide a detailed summary of their experience delivering care to the first two Ebola-infected patients admitted to the biocontainment unit (BCU) at the University of Nebraska Medical Center (UNMC), with a focus on the planning and provision of critical care services to such patients. The authors focus on all aspects of critical care services for patients infected with high-consequence pathogens, such as intensivist training and staffing, practical considerations in the performance of invasive procedures, and pre-emptive planning for responding to acute life-threatening events. Several practical issues of caring for critically ill patients are detailed in their review. Communication among key consultant services in the planning phase of high-containment units has been previously emphasized; however, the authors note that inclusion of critical care physicians in training exercises had not until recently been routinely done at UNMC (8). As the scope of care expanded for these patients, the inclusion of critical care providers in the preparation phase prior to the *See also p. 1157. Key Words: biocontainment unit; Ebola virus disease; high-consequence pathogen; intensive care; personal protective equipment Dr. Torabi-Parizi received support for article research from the National Institutes of Health and disclosed government work. Copyright © 2015 by the Society of Critical Care Medicine and Wolters Kluwer Health, Inc. All Rights Reserved. DOI: 10.1097/CCM.0000000000001009
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www.ccmjournal.org
arrival of patients to BCUs was found to be essential. While emphasizing the proper supervised donning and doffing of personal protective equipment (PPE), the performance of any task that requires fine motor dexterity (ie, suturing a central venous catheter in place) in full PPE is challenging. Systematic planning and preparation for nonemergent airway management is essential. Considerations such as the need for heightened PPE to include powered air-purifying respirators given the possible proximity of the operator’s face to the patient’s oral cavity during an intubation attempt, the liberal use of neuromuscular blockade and the preferential use of video over direct laryngoscopy must all be carefully analyzed. Furthermore, the challenge of adequate critical care staffing is reviewed. Initially, the first BCU patient was assigned to one of two critical care teams that cared for other critically ill patients in addition to this patient in the hospital. The intensivist assigned to the BCU patient coordinated care with the primary infectious disease team on a daily basis. However, the lack of a dedicated team was found to be suboptimal, given the extended time needed for proper donning and doffing of PPE. As a result, a dedicated intensivist team was created with the sole responsibility of responding to escalated care needs for the BCU patients. In addition to practical and technical considerations, the authors further provide readers with an overview of the clinical course, and laboratory and physiological data pertaining to the first two Ebola-infected patients who were admitted to UNMC. Substantial gastrointestinal losses and electrolyte imbalance required aggressive electrolyte and fluid replacement. In addition, the complexities of safe handling of samples from these patients made frequent laboratory testing challenging. Acquisition of point-of-care testing made the majority of critical care laboratory assays readily available. Profound nausea and emesis hindered adequate intake, and both patients were given total parenteral nutrition. Finally, the authors also discuss the need to achieve a balance between provider risk and eventual benefit to patients. At UNMC, the medical teams involved had agreed a priori that patients with Ebola virus disease would not receive chest compressions in the event of cardiopulmonary arrest. However, although some have advocated this approach, others have argued for a more individualized assessment of single patient cases in the decision to emergently provide life-saving measures (9–12). In conclusion, Johnson et al (7) emphasize the challenges associated with caring for patients infected with high-consequence June 2015 • Volume 43 • Number 6
Copyright © 2015 by the Society of Critical Care Medicine and Wolters Kluwer Health, Inc. All Rights Reserved.
Editorials
pathogens in a BCU. As with other critically ill patients, a multidisciplinary team approach in the planning and implementation of all phases of care is necessary. This includes rigorous training and stringent adherence to PPE guidelines, as well as an understanding of the technical limitations of critical care in caring for patients infected with high-consequence pathogens.
REFERENCES
1. Kreuels B, Wichmann D, Emmerich P, et al: A case of severe Ebola virus infection complicated by gram-negative septicemia. N Engl J Med 2014; 371:2394–2401 2. Wolf T, Kann G, Becker S, et al: Severe Ebola virus disease with vascular leakage and multiorgan failure: Treatment of a patient in intensive care. Lancet 2014 Dec 19. [Epub ahead of print] 3. Connor MJ Jr, Kraft C, Mehta AK, et al: Successful delivery of RRT in Ebola virus disease. J Am Soc Nephrol 2015; 26:31–37 4. Interim Guidance for Emergency Medical Services (EMS) Systems and 9-1-1 Public Safety Answering Points (PSAPs) for Management of Patients Who Present with Possible Ebola Virus Disease in the United States. Available at: http://www.cdc.gov/vhf/ebola/hcp/interim-guidance-emergency-medical-services-systems-911-public-safety-answering-points-management-patients-known-suspected-united-states.html. Accessed February 20, 2015
5. Ebola Clinical Care Guidelines: a Guide for Clinicians in Canada version 2. Available at: http://www.ammi.ca/media/73235/ Ebola%20Clinical%20Care%20Guidelines%20v2%2028%20 Oct%02014.pdf. Accessed February 20, 2015 6. Infection prevention and control guidance for care of patients in health-care settings, with focus on Ebola. Available at: http://www. who.int/csr/resources/publications/ebola/filovirus_infection_control/en/. Accessed February 20, 2015 7. Johnson DW, Sullivan JN, Piquette CA, et al: Lessons Learned: Critical Care Management of Patients With Ebola in the United States. Crit Care Med 2015; 43:1157–1164 8. Smith PW, Anderson AO, Christopher GW, et al: Designing a biocontainment unit to care for patients with serious communicable diseases: a consensus statement. Biosecur Bioterror 2006; 4:351–365 9. Responding to Ebola: Questions about Resuscitation. Available at:http://www.thehastingscenter.org/Bioethicsforum/Post. aspx?id=7135&blogid=140. Accessed February 20, 2015 10. Should Doctors Deny Ebola Patients CPR? Available at: http://health affairs.org/blog/2014/12/11/should-doctors-deny-ebola-patients-cpr/. Accessed February 20, 2015 11. Ebola Patients and the Ethics of Unilateral Do-Not-Resuscitate Orders. Available at: http://voicesinbioethics.org/2014/11/24/ebolapatients-dnr-orders/. Accessed February 20, 2015 12. Halpern SD, Emanuel EJ: Ethical guidance on the use of life-sustaining therapies for patients with Ebola in developed countries. Ann Intern Med 2015; 162:304–305
Increased Mortality in “Cold Sepsis”: The Result of a Frozen Immune Response?* James N. Fullerton, MD Centre for Clinical Pharmacology Division of Medicine University College London London, United Kingdom
“C
old sepsis” kills: this much is known. Observational studies and data derived from the control arm of randomized controlled trials indicate that between 10% and 20% of patients with sepsis present hypothermic (variably defined as ≤ 35.5–36.5°C) and experience a mortality rate roughly twice that of their pyrexic peers (1–3). Why? Animal data (and some human) suggest that hypothermia is associated with several favorable physiological and hematological characteristics in sepsis including reduced metabolic (oxygen) demand, improved hemodynamics, and ameliorated coagulopathy (4–6). *See also p. 1165. Key Words: hypothermia; immunosuppression; infection; lymphopenia; sepsis Dr. Fullerton received grant support from the Wellcome Trust. He is a Wellcome Trust Clinical Research Training Fellow. The grant covers his salary and consumables and received support for article research from the Wellcome Trust. Copyright © 2015 by the Society of Critical Care Medicine and Wolters Kluwer Health, Inc. All Rights Reserved. DOI: 10.1097/CCM.0000000000000987
Critical Care Medicine
Experimentally, these may even translate into reduced mortality (7). In this issue of Critical Care Medicine, an interesting brief report presented by Drewry et al (8) alludes to an explanation between this seeming paradox. The authors present further analysis of a previously published retrospective observational dataset (9) describing an independent association between early hypothermia (lowest body temperature < 36°C within 24 hr of first positive blood culture) and persistent lymphopenia (absolute lymphocyte count < 1.2 cells per microliter × 103 at day 4 postdiagnosis) in patients with sepsis. In line with previous reports the hypothermic cohort experienced significant excess mortality compared with nonhypothermic controls (50% vs 24.9% at 28 d), a discrepancy that, for the first time, was noted to endure at 1 year. The authors suggest that persistent lymphopenia, concordant with their previous work, represents a biomarker for sepsis-induced immunosuppression in this population and hypothesize that it is this loss of immune competence that accounts for their reduced survival (9). Is there evidence to support this assertion? Lymphopenia presurgery (10), or that persisting post-trauma (11), has already been linked with increased mortality and infective complications. Most relevantly, Inoue et al, (12) exploring age-related differences in sepsis-induced immunological responses, found that “elderly” patients with sepsis (> 65 yr old) had a lower survival rate than those less than 65 years old (60% vs 89% at 3 mo). Although both age-defined septic populations had reduced T cell levels compared with healthy donors (by circa 55%), nonsurvivors, and in www.ccmjournal.org
Copyright © 2015 by the Society of Critical Care Medicine and Wolters Kluwer Health, Inc. All Rights Reserved.
1327
Critical Care Management of Two Patients With Ebola: A Biocontainment Unit Demystified* Parizad Torabi-Parizi, MD Critical Care Medicine Department, Clinical Center National Institutes of Health Bethesda, MD
I
n less than 1 year, during the dramatic rise of Ebola virus disease in Western Africa, the medical community has been required to respond to multiple areas of uncertainty regarding the best treatments for patients and the safety of healthcare workers. For patients repatriated to their home countries in Europe and the United States, the opportunity to provide higher levels of care added a new layer of complexity regarding the safety and appropriateness of invasive procedures (1–3). Several groups have issued practice guidelines for the safe provision of care to patients infected with the Ebola virus (4–6). Detailed reports of the process of delivering intensive care to these patients in resource-rich settings, however, are limited. In this issue of Critical Care Medicine, Johnson et al (7) provide a detailed summary of their experience delivering care to the first two Ebola-infected patients admitted to the biocontainment unit (BCU) at the University of Nebraska Medical Center (UNMC), with a focus on the planning and provision of critical care services to such patients. The authors focus on all aspects of critical care services for patients infected with high-consequence pathogens, such as intensivist training and staffing, practical considerations in the performance of invasive procedures, and pre-emptive planning for responding to acute life-threatening events. Several practical issues of caring for critically ill patients are detailed in their review. Communication among key consultant services in the planning phase of high-containment units has been previously emphasized; however, the authors note that inclusion of critical care physicians in training exercises had not until recently been routinely done at UNMC (8). As the scope of care expanded for these patients, the inclusion of critical care providers in the preparation phase prior to the *See also p. 1157. Key Words: biocontainment unit; Ebola virus disease; high-consequence pathogen; intensive care; personal protective equipment Dr. Torabi-Parizi received support for article research from the National Institutes of Health and disclosed government work. Copyright © 2015 by the Society of Critical Care Medicine and Wolters Kluwer Health, Inc. All Rights Reserved. DOI: 10.1097/CCM.0000000000001009
1326
www.ccmjournal.org
arrival of patients to BCUs was found to be essential. While emphasizing the proper supervised donning and doffing of personal protective equipment (PPE), the performance of any task that requires fine motor dexterity (ie, suturing a central venous catheter in place) in full PPE is challenging. Systematic planning and preparation for nonemergent airway management is essential. Considerations such as the need for heightened PPE to include powered air-purifying respirators given the possible proximity of the operator’s face to the patient’s oral cavity during an intubation attempt, the liberal use of neuromuscular blockade and the preferential use of video over direct laryngoscopy must all be carefully analyzed. Furthermore, the challenge of adequate critical care staffing is reviewed. Initially, the first BCU patient was assigned to one of two critical care teams that cared for other critically ill patients in addition to this patient in the hospital. The intensivist assigned to the BCU patient coordinated care with the primary infectious disease team on a daily basis. However, the lack of a dedicated team was found to be suboptimal, given the extended time needed for proper donning and doffing of PPE. As a result, a dedicated intensivist team was created with the sole responsibility of responding to escalated care needs for the BCU patients. In addition to practical and technical considerations, the authors further provide readers with an overview of the clinical course, and laboratory and physiological data pertaining to the first two Ebola-infected patients who were admitted to UNMC. Substantial gastrointestinal losses and electrolyte imbalance required aggressive electrolyte and fluid replacement. In addition, the complexities of safe handling of samples from these patients made frequent laboratory testing challenging. Acquisition of point-of-care testing made the majority of critical care laboratory assays readily available. Profound nausea and emesis hindered adequate intake, and both patients were given total parenteral nutrition. Finally, the authors also discuss the need to achieve a balance between provider risk and eventual benefit to patients. At UNMC, the medical teams involved had agreed a priori that patients with Ebola virus disease would not receive chest compressions in the event of cardiopulmonary arrest. However, although some have advocated this approach, others have argued for a more individualized assessment of single patient cases in the decision to emergently provide life-saving measures (9–12). In conclusion, Johnson et al (7) emphasize the challenges associated with caring for patients infected with high-consequence June 2015 • Volume 43 • Number 6
Copyright © 2015 by the Society of Critical Care Medicine and Wolters Kluwer Health, Inc. All Rights Reserved.
Editorials
pathogens in a BCU. As with other critically ill patients, a multidisciplinary team approach in the planning and implementation of all phases of care is necessary. This includes rigorous training and stringent adherence to PPE guidelines, as well as an understanding of the technical limitations of critical care in caring for patients infected with high-consequence pathogens.
REFERENCES
1. Kreuels B, Wichmann D, Emmerich P, et al: A case of severe Ebola virus infection complicated by gram-negative septicemia. N Engl J Med 2014; 371:2394–2401 2. Wolf T, Kann G, Becker S, et al: Severe Ebola virus disease with vascular leakage and multiorgan failure: Treatment of a patient in intensive care. Lancet 2014 Dec 19. [Epub ahead of print] 3. Connor MJ Jr, Kraft C, Mehta AK, et al: Successful delivery of RRT in Ebola virus disease. J Am Soc Nephrol 2015; 26:31–37 4. Interim Guidance for Emergency Medical Services (EMS) Systems and 9-1-1 Public Safety Answering Points (PSAPs) for Management of Patients Who Present with Possible Ebola Virus Disease in the United States. Available at: http://www.cdc.gov/vhf/ebola/hcp/interim-guidance-emergency-medical-services-systems-911-public-safety-answering-points-management-patients-known-suspected-united-states.html. Accessed February 20, 2015
5. Ebola Clinical Care Guidelines: a Guide for Clinicians in Canada version 2. Available at: http://www.ammi.ca/media/73235/ Ebola%20Clinical%20Care%20Guidelines%20v2%2028%20 Oct%02014.pdf. Accessed February 20, 2015 6. Infection prevention and control guidance for care of patients in health-care settings, with focus on Ebola. Available at: http://www. who.int/csr/resources/publications/ebola/filovirus_infection_control/en/. Accessed February 20, 2015 7. Johnson DW, Sullivan JN, Piquette CA, et al: Lessons Learned: Critical Care Management of Patients With Ebola in the United States. Crit Care Med 2015; 43:1157–1164 8. Smith PW, Anderson AO, Christopher GW, et al: Designing a biocontainment unit to care for patients with serious communicable diseases: a consensus statement. Biosecur Bioterror 2006; 4:351–365 9. Responding to Ebola: Questions about Resuscitation. Available at:http://www.thehastingscenter.org/Bioethicsforum/Post. aspx?id=7135&blogid=140. Accessed February 20, 2015 10. Should Doctors Deny Ebola Patients CPR? Available at: http://health affairs.org/blog/2014/12/11/should-doctors-deny-ebola-patients-cpr/. Accessed February 20, 2015 11. Ebola Patients and the Ethics of Unilateral Do-Not-Resuscitate Orders. Available at: http://voicesinbioethics.org/2014/11/24/ebolapatients-dnr-orders/. Accessed February 20, 2015 12. Halpern SD, Emanuel EJ: Ethical guidance on the use of life-sustaining therapies for patients with Ebola in developed countries. Ann Intern Med 2015; 162:304–305
Increased Mortality in “Cold Sepsis”: The Result of a Frozen Immune Response?* James N. Fullerton, MD Centre for Clinical Pharmacology Division of Medicine University College London London, United Kingdom
“C
old sepsis” kills: this much is known. Observational studies and data derived from the control arm of randomized controlled trials indicate that between 10% and 20% of patients with sepsis present hypothermic (variably defined as ≤ 35.5–36.5°C) and experience a mortality rate roughly twice that of their pyrexic peers (1–3). Why? Animal data (and some human) suggest that hypothermia is associated with several favorable physiological and hematological characteristics in sepsis including reduced metabolic (oxygen) demand, improved hemodynamics, and ameliorated coagulopathy (4–6). *See also p. 1165. Key Words: hypothermia; immunosuppression; infection; lymphopenia; sepsis Dr. Fullerton received grant support from the Wellcome Trust. He is a Wellcome Trust Clinical Research Training Fellow. The grant covers his salary and consumables and received support for article research from the Wellcome Trust. Copyright © 2015 by the Society of Critical Care Medicine and Wolters Kluwer Health, Inc. All Rights Reserved. DOI: 10.1097/CCM.0000000000000987
Critical Care Medicine
Experimentally, these may even translate into reduced mortality (7). In this issue of Critical Care Medicine, an interesting brief report presented by Drewry et al (8) alludes to an explanation between this seeming paradox. The authors present further analysis of a previously published retrospective observational dataset (9) describing an independent association between early hypothermia (lowest body temperature < 36°C within 24 hr of first positive blood culture) and persistent lymphopenia (absolute lymphocyte count < 1.2 cells per microliter × 103 at day 4 postdiagnosis) in patients with sepsis. In line with previous reports the hypothermic cohort experienced significant excess mortality compared with nonhypothermic controls (50% vs 24.9% at 28 d), a discrepancy that, for the first time, was noted to endure at 1 year. The authors suggest that persistent lymphopenia, concordant with their previous work, represents a biomarker for sepsis-induced immunosuppression in this population and hypothesize that it is this loss of immune competence that accounts for their reduced survival (9). Is there evidence to support this assertion? Lymphopenia presurgery (10), or that persisting post-trauma (11), has already been linked with increased mortality and infective complications. Most relevantly, Inoue et al, (12) exploring age-related differences in sepsis-induced immunological responses, found that “elderly” patients with sepsis (> 65 yr old) had a lower survival rate than those less than 65 years old (60% vs 89% at 3 mo). Although both age-defined septic populations had reduced T cell levels compared with healthy donors (by circa 55%), nonsurvivors, and in www.ccmjournal.org
Copyright © 2015 by the Society of Critical Care Medicine and Wolters Kluwer Health, Inc. All Rights Reserved.
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