Author: reuben

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Paxlovid Patient/Caregiver Fact Sheet

Paxlovid Healthcare Professionals Fact Sheet

Paxlovid FDA Checklist [updated Oct 2022]

molnupiravir EUA & patient info

Maimonides Medical Center (MMC) is Brooklyn’s largest hospital, an academic quaternary care center with, in normal times, 711 total beds, 66 intensive care beds, and an Emergency Department that treats approximately 120,000 patients per year.

On March 9, the first patient with a novel coronavirus infection was admitted to MMC. At its peak, on April 9, there were 471 patients with confirmed or suspected COVID-19 admitted to the hospital, with 139 patients designated to be occupying a critical care bed and 184 patients receiving mechanical ventilation. On May 7, after 2 months of strict physical distancing across the city, the hospital discharged its 1000th COVID-19 patient, as the surge of coronavirus cases that is estimated to have killed 25,000 New Yorkers¹ was drawing to a close.

From April 6 to May 3, in response to the rapidly-evolving approach to treatment of severe COVID-19 infection, and to accommodate an unprecedented demand for critical care resources at our institution, we implemented a novel patient care program, the Emergency Department Admitting Team (EDAT), which adapted intensive care paradigms to Emergency Department logistics, staffing, and flow. Every patient admitted to the EDAT was followed to the conclusion of their hospital course; the development of this unit and patient outcomes resulting from its execution are presented here.

In the last week of March and first week of April 2020, hospitals across New York City were overwhelmed with critically ill COVID-19 patients, many of whom had unprecedented oxygen requirements. Endotracheal intubation was the dominant treatment modality during the initial phase of the NYC surge,^2-4 and ICU capacity was quickly saturated. Frontline providers pivoted to noninvasive oxygenation strategies,^5-7 but these patients required a level of care exceeding the capabilities of a general medical ward. At the same time, emergency department (ED) arrivals for conditions not related to COVID-19 dropped precipitously.

In response, we determined that the safest way to care for critically ill COVID-19 patients who could not be adequately oxygenated on low-flow oxygen (i.e. conventional nasal cannula or face mask) but could be stabilized on noninvasive ventilation (NIV) or high-flow nasal cannula (HFNC), was that they should remain in the ED and cared for longitudinally by the ED team. Because of these patients’ rapidly evolving (and poorly understood) critical illness, holding them downstairs was tantamount to creating a makeshift intensive care unit in the ED.

Administrative logistics demanded that patients receiving ongoing care in the emergency department be formally admitted to the hospital; we were therefore enjoined to admit these patients to ourselves and therefore formed the Emergency Department Admitting Team. At our institution, Emergency Physicians are afforded admitting privileges which had not been exercised previously. A geographic space within the high acuity zone of the department was designated for EDAT patients, all staff entering the zone were required to don full personal protective equipment. Any patient requiring high acuity care not thought to be infected with coronavirus was cared for in a different area that had previously been a low acuity zone, but which was subsequently equipped for resuscitation.

The EDAT was staffed entirely by Emergency Medicine attendings, only one of whom was board-certified in both Emergency Medicine and Critical Care (C.K.S.), and Emergency Medicine residents, in 12 hour shifts. We scheduled providers in blocks of 2, 3, or 4 consecutive shifts (12 hours on, 12 hours off) to facilitate continuity of care. At its peak volume, the EDAT was staffed by 2 attendings and 3 residents per shift. Emergency nursing, technician, and clerical staffing was unchanged compared to usual staffing for the zone, with far higher patient:nurse ratios than allowable in a proper ICU, as all other critical care resources were engaged on the units and were not available to assist in the direct care of these patients.

The criterion for EDAT admission was HFNC therapy, which had been used on a smaller scale in our institution for several years. HFNC was in most cases set up by respiratory therapy. Patients who failed HFNC and required endotracheal intubation (ETI) were transferred to a conventional inpatient service; however many of these patients were delayed in their ascent upstairs and while physically located in the ED remained under the care of the EDAT. Patients who improved on HFNC and could be transitioned to low-flow oxygen were transferred to a lower acuity inpatient service for continued care.

During the study period, there were no established specific therapies for COVID-19. Treatment protocols changed rapidly and were devised by departmental and hospital consensus. The EDAT adopted a hybrid of intensive care and emergency department paradigms; for example, patients were evaluated and transfer of care occurred using a systems-based format, but the primary activity of the physician team was to reassess patients constantly by continuous rounding, as is typical in EM practice.

The focus of treatment for most patients was maintenance and titration of the HFNC, prone positioning, chest physiotherapy, and other forms of supportive care. Particular effort was required to keep family members, who were not allowed in the hospital for risk of contagion, apprised of their loved one’s status.

After admission to the EDAT, documentation was performed on the inpatient electronic health record (EHR), which at MMC is a different platform than the ED EHR. All patients admitted to the EDAT were identified on a daily report and their clinical course abstracted from the EHR onto a structured database by 2 research fellows and 7 emergency medicine residents. The study was approved by the MMC institutional review board.

 

 

From April 6 to May 3, 2020, 90 patients were admitted to the EDAT. Of these, 10 patients did not have curative goals of care (i.e. had DNR/DNI orders), 5 patients were transferred from an outside institution, and 6 were determined not to have COVID-19; these 21 patients were excluded from this analysis, as well as a single patient who at the time of this writing was still in ICU after over two months of mechanical ventilation and ECMO, leaving a cohort of 68 patients. All 10 DNR/DNI patients and all 5 transfer patients died; 4 of 6 non-COVID patients cared for by the EDAT died and 2 were discharged. The average number of patients admitted to the EDAT over the study period of 28 days was 11, with a maximum of 23 patients on April 12, 2020.

Results are presented in Table 1. The average age of the 68 patients treated on the EDAT was 65.6 years; 63% of patients were male. 19 patients (28%) were discharged from the hospital and 49 (72%) expired. Of the 49 patients that did not survive, 7 died in the emergency department, 15 died on the medical wards, and 27 died in the ICU. Discharged patients were on average 13 years younger than patients who expired. Hospital length of stay was similar between the two groups.

There were significant differences between the groups in the use of different forms of respiratory support, with discharged patients more likely to receive low-flow oxygen and expired patients more likely to be treated with mechanical ventilation; this likely reflects illness severity rather than negative or positive effects of the oxygenation modality. HFNC was strongly favored at our center over NIV in patients who could not be stabilized on low-flow oxygen, and HFNC use, the focus of EDAT therapy, was similar between the two groups.

Discharged patients were significantly more likely to be treated with convalescent plasma and tocilizumab, with expired patients more likely to be treated with hydroxychloroquine and remdesivir. Because the mortality among EDAT patients decreased in the last half of the study period (10 out of 19 discharged patients presented after April 21), and because therapy choices were often guided by illness severity among rapidly shifting trends in COVID-19 treatment (e.g. hydroxychloroquine fell out of favor), we do not draw causal inferences from these trends. Remdesivir was restricted to critically ill, intubated patients and could only be given via an experimental protocol. Other agents, also part of research protocols, were not similarly limited to intubated patients.

 

 

The surge of COVID-19 patients in New York City from late March to April 2020 imposed a crisis of emergency care, the full magnitude and impact of which will require years to measure and reckon with. The crisis was caused predominantly by a deficit in critical care capacity not experienced domestically in modern times, compounded by inadequate testing capability and scientific uncertainty around a novel disease. This uncertainty included a nearly complete absence of data to inform treatment decisions and extended to shifting theories of virus transmissibility and lethality, generating fears magnified by nationwide shortages of personal protective equipment.

The first wave of coronavirus arrivals were mostly stable patients with flu-like symptoms who requested diagnostic testing. During that early phase of the surge, the challenge for Emergency Medicine was to determine which patients required ancillary studies (including COVID-19 testing, which was usually not available) while maintaining the type of infectious isolation precautions customary in normal times. “Hot” and “cold” zones were set up, as well as detached screening/testing locations, and many ambulatory patients were assessed and released without ever entering the ED.

Community spread in early and mid-March advanced unchecked by the use of masks or physical distancing, mitigation strategies not yet embraced by the public. The natural history of the virus therefore quickly replaced the worried well with progressively ill patients who required escalating levels of respiratory support. The city entered lockdown on March 22, and the wide spectrum of illnesses typically seen by emergency clinicians was reduced to steadily worsening presentations of a single disease.

Based on the experience of the earliest outbreaks in China and Italy, emergency physicians adopted a strategy of intubate early, which stipulated that patients who were not stabilized by low-flow oxygen (nasal cannula less than 6 liters per minute) should be managed with intubation and mechanical ventilation.⁵ This strategy arose from the rapidly progressive oxygen requirements observed in the earliest days of the pandemic, as well as from concerns that noninvasive forms of advanced oxygenation–NIV and HFNC–posed an unacceptable risk of aerosolization of viral particles. However, preliminary data emerging from besieged hospitals in Asia and Europe showed high mortality in intubated patients.^8-12 Furthermore, as the magnitude of disease prevalence came into view, it was clear that critical care resources would quickly be exhausted if intermediate oxygenation modalities were not deployed.

Providers across the city therefore moved to NIV and HFNC therapies in the hope that ICU resources would be conserved and patient outcomes would be improved.^2,5 Unsedated patients were also able to participate in awake proning, which was demonstrated to improve oxygenation and (at least temporarily) prevent progression to intubation.^13-15 These patients were initially admitted to general medicine wards; however, it was quickly learned that their dependence on oxygen was so profound, their disease so unpredictable, and their physiology so fragile that they could not be safely managed behind the closed doors of a typical inpatient unit.

Given the perceived harms of early intubation and the citywide shortage of critical care beds, the EDAT was created to make use of the only available venue to provide acceptable monitoring and treatment of the ongoing surge of patients with severe COVID-19. The team was developed to apply continuous intensive care within a framework designed for, and by clinicians trained in, episodic emergency care. EM attendings and residents were scheduled in shift blocks, with a single intensive care-trained emergency physician providing daily supervision, consultation, and administration. This allowed maximal continuity of patient care within an ED staffing model, as well as rapid reorientation to quickly shifting treatment principles.

EDAT providers contended with myriad challenges. Inpatient-type care relies on a skillset and mindset unlike the focused, compartmentalized attention required of emergency clinicians, and longitudinal management of critically ill patients demands mastery of an even more specialized expertise normally acquired in a 2-year fellowship.¹⁶ Usual hospital processes were constantly revised to accommodate repurposed spaces, services and personnel. Clinical testing and treatment protocols changed almost every day. Many critical supplies, especially respiratory equipment, were scarce or unavailable. Providers carried out their tasks using foreign ordering and documentation pathways within an EHR that had to be learned immediately and without training. Additionally, all staff worked with rapidly deployed, unfamiliar equipment, most notably recently acquired ventilators, in addition to novel devices and workflows to reduce viral contagion.^17-19 The greatest challenge was the emotional toll of caring for scores of patients suffering from a disease for which there were no known effective treatments and who therefore often deteriorated despite all efforts.

EDAT treatment was centered on the use of noninvasive oxygenation modalities, with most patients managed using HFNC according to a departmental protocol. (Figure 1) Though every patient admitted to EDAT would have otherwise been intubated and placed on mechanical ventilation, and therefore those patients who returned to health may have been well served or even saved by a delayed intubation approach, most EDAT patients ultimately were intubated and the majority of these patients expired. Outcomes did improve over the course of the study period, which, in addition to decreased illness severity, may be the result of one or a combination of factors. As the surge continued, providers developed more comfort with profound hypoxemia and with the assiduous attention to continuous high-flow oxygen therapy that allowed intubation–especially the rushed intubation procedures resulting from patients accidentally coming off oxygen–to be delayed or avoided. Crystalloid infusions, therapeutic anticoagulation (as opposed to prophylaxis), dexmedetomidine (for anxiolysis), and chest physiotherapy were used more liberally over time. Perhaps most importantly, EDAT workflows that were completely new to the department and implemented without the opportunity for vetting or training became more functional and less prone to error as ED staff gained experience and expertise in managing a cohort of critically ill patients dependent on uninterrupted high-flow oxygen.

The optimal oxygenation technique for patients with severe COVID-19 remains controversial and informed by few experimental data.^20-22 In our cohort of 68 patients treated according to a HFNC-first paradigm, 18 patients were successfully managed without mechanical ventilation and discharged. However, of the remaining 50 patients who were intubated, only 1 survived. Whether the alarmingly high mortality rates of intubated patients seen in this series (and across all of New York City^23-27) during the surge was due to mistimed application of mechanical ventilation, due to other errors in treatments offered or treatments not offered, due to disease severity, or due to the mass casualty dynamics that prevented optimal critical care, is uncertain.

Reuben J. Strayer, MD

Cameron Kyle-Sidell, MD

Daniel Dove, MD

Ashley R. Davis, MD

Eitan Dickman, MD

John P. Marshall, MD

 

The authors acknowledge the following physicians for their assistance in data collection: Humaira Ali, Elizabeth Fruchter, Suman Gupta, Michelle Haimowitz, Tome Levy, Meagan Murphy, Eric Quinn, Kestrel Reopelle, David Shang, Maisa Siddique, Kazi Sumon, Sabena Vaswani and Jung Yum.

 We wish to further acknowledge and salute the Emergency Department staff of Maimonides Medical Center, all of whom confronted and overcame previously unimaginable challenges to providing care to a Brooklyn community struck by the worst public health disaster in a century.

Photographs courtesy of Duncan Grossman, DO. 

 

 

 

References

1. Weinberger DM, Chen J, Cohen T, et al. Estimation of Excess Deaths Associated With the COVID-19 Pandemic in the United States, March to May 2020 [published online ahead of print, 2020 Jul 1]. JAMA Intern Med. 2020;e203391. doi:10.1001/jamainternmed.2020.3391

2. Patel M, Chowdhury J, Mills N, Marron R, Gangemi A, Dorey-Stein Z, Yousef I, Tragesser L, Giurintano J, Gupta R, Rali P. ROX Index Predicts Intubation in Patients with COVID-19 Pneumonia and Moderate to Severe Hypoxemic Respiratory Failure Receiving High Flow Nasal Therapy. medRxiv. 2020 July 3.

3. Ziehr DR, Alladina J, Petri CR, et al. Respiratory Pathophysiology of Mechanically Ventilated Patients with COVID-19: A Cohort Study. Am J Respir Crit Care Med. 2020;201(12):1560-1564. doi:10.1164/rccm.202004-1163LE

4. Zareifopoulos N, Lagadinou M, Karela A, Platanaki C, Karantzogiannis G, Velissaris D. Management of COVID-19: the risks associated with treatment are clear, but the benefits remain uncertain. Monaldi Arch Chest Dis. 2020;90(2):10.4081/monaldi.2020.1342. Published 2020 May 5. doi:10.4081/monaldi.2020.1342

5. Rola P, Farkas J, Spiegel R, et al. Rethinking the early intubation paradigm of COVID-19: time to change gears?. Clin Exp Emerg Med. 2020;7(2):78-80. doi:10.15441/ceem.20.043

6. Berlin DA, Gulick RM, Martinez FJ. Severe Covid-19 [published online ahead of print, 2020 May 15]. N Engl J Med. 2020;10.1056/NEJMcp2009575. doi:10.1056/NEJMcp2009575

7. Alhazzani W, Møller MH, Arabi YM, et al. Surviving Sepsis Campaign: Guidelines on the Management of Critically Ill Adults with Coronavirus Disease 2019 (COVID-19). Crit Care Med. 2020;48(6):e440-e469. doi:10.1097/CCM.0000000000004363

8. Yang X, Yu Y, Xu J, et al. Clinical course and outcomes of critically ill patients with SARS-CoV-2 pneumonia in Wuhan, China: a single-centered, retrospective, observational study [published correction appears in Lancet Respir Med. 2020 Apr;8(4):e26]. Lancet Respir Med. 2020;8(5):475-481. doi:10.1016/S2213-2600(20)30079-5

9. Wu Z, McGoogan JM. Characteristics of and Important Lessons From the Coronavirus Disease 2019 (COVID-19) Outbreak in China: Summary of a Report of 72 314 Cases From the Chinese Center for Disease Control and Prevention [published online ahead of print, 2020 Feb 24]. JAMA. 2020;10.1001/jama.2020.2648. doi:10.1001/jama.2020.2648

10. Grasselli G, Zangrillo A, Zanella A, et al. Baseline Characteristics and Outcomes of 1591 Patients Infected With SARS-CoV-2 Admitted to ICUs of the Lombardy Region, Italy [published online ahead of print, 2020 Apr 6]. JAMA. 2020;323(16):1574-1581. doi:10.1001/jama.2020.5394

11. Zhou F, Yu T, Du R, et al. Clinical course and risk factors for mortality of adult inpatients with COVID-19 in Wuhan, China: a retrospective cohort study [published correction appears in Lancet. 2020 Mar 28;395(10229):1038]

12. Barrasa H, Rello J, Tejada S, et al. SARS-CoV-2 in Spanish Intensive Care Units: Early experience with 15-day survival in Vitoria [published online ahead of print, 2020 Apr 9]. Anaesth Crit Care Pain Med. 2020;S2352-5568(20)30064-3. doi:10.1016/j.accpm.2020.04.001

13. Thompson AE, Ranard BL, Wei Y, Jelic S. Prone Positioning in Awake, Nonintubated Patients With COVID-19 Hypoxemic Respiratory Failure [published online ahead of print, 2020 Jun 17]. JAMA Intern Med. 2020;e203030. doi:10.1001/jamainternmed.2020.3030

14. Coppo A, Bellani G, Winterton D, et al. Feasibility and physiological effects of prone positioning in non-intubated patients with acute respiratory failure due to COVID-19 (PRON-COVID): a prospective cohort study [published online ahead of print, 2020 Jun 19]. Lancet Respir Med. 2020;S2213-2600(20)30268-X. doi:10.1016/S2213-2600(20)30268-X

15. Caputo ND, Strayer RJ, Levitan R. Early Self-Proning in Awake, Non-intubated Patients in the Emergency Department: A Single ED’s Experience During the COVID-19 Pandemic. Acad Emerg Med. 2020;27(5):375-378. doi:10.1111/acem.13994

16. Jayaprakash N, Pflaum-Carlson, Gardner-Gray J, et al. Critical Care Delivery Solutions in the Emergency Department: Evolving Models in Caring for ICU Boarders [published online ahead of print, 2020 Jul 8]. Ann Emerg Med. 2020;S0196-0644(20)30349-8. doi:10.1016/j.annemergmed.2020.05.007

17. Ponnappan KT, Sam AF, Tempe DK, Arora MK. Intubation box in the current pandemic – helps or hinders? [published online ahead of print, 2020 Jun 30]. Anaesth Crit Care Pain Med. 2020;S2352-5568(20)30127-2. doi:10.1016/j.accpm.2020.06.011

18. Malysz M, Dabrowski M, Böttiger BW, et al. Resuscitation of the patient with suspected/confirmed COVID-19 when wearing personal protective equipment: A randomized multicenter crossover simulation trial [published online ahead of print, 2020 May 18]. Cardiol J. 2020;10.5603/CJ.a2020.0068. doi:10.5603/CJ.a2020.0068

19. Lau YF, Wei W, Lau CP. Are stethoscopes risky in COVID-19?. Postgrad Med J. 2020;96(1137):431. doi:10.1136/postgradmedj-2020-138085

20. Tobin MJ, Laghi F, Jubran A. Caution about early intubation and mechanical ventilation in COVID-19. Ann Intensive Care. 2020;10(1):78. Published 2020 Jun 9. doi:10.1186/s13613-020-00692-6

21. Marini JJ, Gattinoni L. Management of COVID-19 Respiratory Distress [published online ahead of print, 2020 Apr 24]. JAMA. 2020;10.1001/jama.2020.6825. doi:10.1001/jama.2020.6825

22. Gattinoni L, Marini JJ, Busana M, Chiumello D, Camporota L. Spontaneous breathing, transpulmonary pressure and mathematical trickery. Ann Intensive Care. 2020;10(1):88. Published 2020 Jul 8. doi:10.1186/s13613-020-00708-1

23. Richardson S, Hirsch JS, Narasimhan M, et al. Presenting Characteristics, Comorbidities, and Outcomes Among 5700 Patients Hospitalized With COVID-19 in the New York City Area [published online ahead of print, 2020 Apr 22] [published correction appears in doi: 10.1001/jama.2020.7681]. JAMA. 2020;323(20):2052-2059. doi:10.1001/jama.2020.6775

24. Petrilli CM, Jones SA, Yang J, et al. Factors associated with hospital admission and critical illness among 5279 people with coronavirus disease 2019 in New York City: prospective cohort study. BMJ. 2020;369:m1966. Published 2020 May 22. doi:10.1136/bmj.m1966

25. Goyal P, Choi JJ, Pinheiro LC, et al. Clinical Characteristics of Covid-19 in New York City. N Engl J Med. 2020;382(24):2372-2374. doi:10.1056/NEJMc2010419

26. Paranjpe I, Russak A, De Freitas JK, et al. Clinical Characteristics of Hospitalized Covid-19 Patients in New York City. Preprint. medRxiv. 2020;2020.04.19.20062117. Published 2020 Apr 23. doi:10.1101/2020.04.19.20062117

27. Gayam V, Chobufo MD, Merghani MA, Lamichanne S, Garlapati PR, Adler MK. Clinical characteristics and predictors of mortality in African-Americans with COVID-19 from an inner-city community teaching hospital in New York [published online ahead of print, 2020 Jul 16]. J Med Virol. 2020;10.1002/jmv.26306. doi:10.1002/jmv.26306