What a difference two months make! As a medical community and a society, we have collectively witnessed a significant evolution of knowledge commensurate to the discovery and widespread dissemination of a new disease. Asymptomatic transmission is now accepted as reality with a clear mechanism (N Engl J Med April 24, 2020). Testing is more widely available, yet in many forms with varying degrees of accuracy. Hydroxychloroquine is not the magic bullet that we hoped for. In fact, evidence is mounting that the indiscriminate and irrational use of this drug may contribute to an increased number of cardiac events.
For example, a recent report from patients treated in New York showed that the risk of in-hospital cardiac arrests doubles with the use of hydroxychloroquine and azithromycin in combination compared to no use of these agents (JAMA May11, 2020). This, combined with no outcome benefit with these drugs, has resulted in a rapid practice change in most parts of the world. This is a prime depiction of the dynamic nature of the evolution of evidence with the pandemic – what is evidence and best practice today may not be the same a month later.
Pattern with clinical presentation
COVID-19 has posed unique challenges to the care of patients in the critical care, perioperative, inpatient, and community settings (Anesth Analg May 7, 2020). The population of patients cared for in the ICU has a diverse set of needs that commonly pertain to several key areas, including mechanical ventilation, renal replacement therapy, hemodynamic stability, and coagulopathy, among others.
There now appears to be a pattern emerging with the clinical presentation of COVID-19 infection, with a period of convalescence prior to requiring hospitalization due to increased work of breathing or other symptoms. Once a significant oxygen requirement is noted, prone positioning has been found to be extremely important in the care of these patients. Historically, the critical care world generally considered prone positioning to be a way to reduce mortality in mechanically ventilated patients with ARDS, but we have seen over time that prone positioning is helpful long before intubation in COVID-19 and can stave off many of the more challenging aspects of care when patients require respiratory support.
Additionally, since COVID-19-induced lung disease frequently presents with normal lung compliance, a patient may not be tachypneic and have a relatively low work of breathing even when oxygenation is poor when compared to other forms of acute respiratory failure more traditionally seen in the acute care setting. These “happy hypoxic” folks are therefore tricky to manage, and it takes skill and clinical prowess on the part of the intensivist to know when to intervene with endotracheal intubation. An important problem is that mechanical ventilation seems to have an association with worsening clinical condition, beyond what may be obvious. Though in the absence of an appropriate denominator, we may not be in place to put a clear figure on this mortality number on mechanical ventilation at the current time (Am J Respir Crit Care Med May 13, 2020). Once these patients are intubated, they frequently need mechanical ventilation for one to three weeks. This clinical picture is sometimes referred to as COVID-19-induced ARDS, or “CARDS,” in the literature (Crit Care Med May 13, 2020). During this prolonged time on mechanical ventilation, there are opportunities for concomitant infections with traditional nosocomial organisms such as Pseudomonas aeruginosa or MRSA. The ongoing care of these patients and prevention of nosocomial complications is a point of emphasis for critical care teams caring for these patients.
In addition, there is a pattern of illness wherein a period of relative stability during the first week or so may be followed by a fairly dramatic spiral into multi-system organ failure, associated with a sharp and disproportionate rise in inflammatory markers such as D-dimer, C-reactive protein, IL-6, ferritin, LDH, and others (Lancet March 28, 2020). Some of these are now a therapeutic target for drugs being used or under investigation (Biomed Pharmacother May 14, 2020). Organ failure here seems to be a combination of hemodynamic (COVID-induced myocardial injury) and renal shutdown. Hemodynamic failure may be particularly challenging in that it may be a combination of traditional high-output septic shock and COVID-induced myocardial injury generally manifested as cardiogenic shock. The use of appropriate afterload increasing agents, inotropes, newer vasopressors, and the connection with the renin-angiotensin modulating drugs have all been questioned (Hypertension Research April 27, 2020; Crit Care 2020;24:136).
Respiratory failure that is unresponsive to oxygenation and lung protection via conventional mechanical ventilation, with adjunctive therapy, also brings several patients to the point of using extra corporeal membrane oxygenation (ECMO), usually with a veno-venous cannulation. While this has raised several ethical conundrums, most centers supporting these systems have attempted to formulate guidelines for patient selection that are not far removed from those promulgated by the extra corporeal life support (ELSO) group. The next challenge after prolonged mechanical ventilation with or without ECMO is liberation from these devices, where the need for a tracheostomy, and the ask for performing the procedure safely and in a timely manner, has stressed systems.
COVID-19 and coagulation
COVID-19 also appears to be a disorder of coagulation, and indeed has been described by some as an ongoing endothelial inflammation. Hence, the need for aggressive anticoagulation in this population appears to be clear; however, there is still evolution pertaining to how much anticoagulation is needed and for how long. A low-grade DIC and localized pulmonary thrombotic microangiography results clinically in unrecognized or delayed diagnosed venous or arterial thromboembolic events, sometimes with disastrous consequences. Following D-dimer, platelet count, and aPTT several times a week is a common strategy, with escalation of care when signs of deviation from the norm occur. Concern about causing bleeding has always been a consideration, but unless there is a clinical reason to be concerned, anticoagulation is generally pursued. Early non-randomized data suggests improved outcomes in those with more aggressive anticoagulation regimens (J Thromb Haemost 2020;18:1094-99).
The overall goals on coagulation remain a moving target, and we hope that improved scientific investigation will help standardize care and at some stage help develop guidelines to recommend appropriate therapy.
Chronic co-morbidities can have a negative effect on the outcomes of COVID-19 patients, with hypertension, cardiovascular disease, chronic kidney disease, and diabetes being associated with increased mortality (Research (Wash DC) April 19, 2020). Knowing that older individuals carry most of these comorbid conditions, initial data from China labelled COVID-19 as a disease with poor prognosis in that age group. However, the U.S. experience has been different, and most data here shows that the young are not entirely spared. The mortality rate of COVID-19 appears to vary widely based on the country (see figure, page 8). Results such as these should be interpreted with some skepticism; to accurately determine the case fatality rate, full knowledge of the infection rate must be obtained. As testing is not universally available for the entire community, a true incidence is not known; therefore, a true case fatality rate cannot be calculated. It is likely that the case fatality rate in the U.S. is lower, but this is not certain. Patients who require operative intervention and who are simultaneously infected with COVID-19 have generally been found to have high mortality rates, sometimes in excess of 25% (Surg Infect (Larchmt) May 13, 2020). This makes the pre-operative testing very important in achieving safe anesthesia care as elective cases resume in the U.S.
A first step in understanding this illness is the need for better real-time data dashboards. One such effort is the Society of Critical Care Medicine's (SCCM's) Viral Infection and Respiratory Illness Universal Study (VIRUS) registry, with the aim of a real-time COVID-19 registry of current ICU and hospital care patterns to allow evaluation of safety and observational effectiveness of COVID-19 practices. This effort has resulted in a live dashboard that may be accessed at sccmcovid19.org.
Similarly, the ELSO group has established a very useful ECMO registry. These tools will be essential as we attempt to develop mortality and morbidity prediction models in the near future. One such model has already been developed using data from China, but given the tremendous variability observed between different countries with regard to the nature and outcomes of this illness, it is likely that more country-specific tools will be needed (JAMA Intern Med May 12, 2020).
In addition, data that focused on socio-economic and geographic determinants of disease outcomes – air-travel, population density, nursing home numbers, and racial ethnic numbers – need to be factored into future predictive models.
COVID-19 stretched us thin and exposed gaps in our health care model. Fortunately, we as a community of anesthesiologists rose to the occasion and led from the front within and outside the OR and ICU. With the utilization of resources such as the COVID Activated Emergency Scaling of Anesthesiology Responsibilities (CAESAR) ICU initiative, this can be done (Anesth Analg May 7, 2020). This free tool has now been downloaded more than 100,000 times by teams around the world (www.asahq.org/in-the-spotlight/coronavirus-covid-19-information/caesar).
“COVID-19 stretched us thin and exposed gaps in our health care model. Fortunately, we as a community of anesthesiologists rose to the occasion and led from the front within and outside the OR and ICU.”
As time progresses, our medical community should be prepared to have an ongoing new normal in the ICU and OR. There will be a need to determine strategies for long-term management of patients who had severe COVID-19 infection. Since more than 40% of ICU patients have ongoing medical needs and 20% have multiple hospital re-admissions, we should be prepared for a similar natural history in the COVID-19 population. Such patients could frequently present to the OR for repeated surgeries related to their medical co-morbidities; anesthesiologists would again be called upon to provide safe and innovative care for COVID-19 patients.