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March 31, 2020
IMPROVING SURVIVAL OF COVID-19 PATIENTS
THE PRACTICAL MANAGEMENT OF ARDS
Tom Schneider, MD
Board Certified in Pulmonary
Critical Care Medicine and Internal
I have been a practicing Pulmonary and Critical Care physician for more than 30 years and I have worked with the early generation of ventilators from the 1980’s through the current microprocessor and software driven models of today. I have endeavored to study the best way to ventilate patients and the methods that yielded optimal outcomes. I am writing this article to share this information with the medical community in the hope that it may save lives during the current pandemic of COVID-19.
A Landmark Study
Prior to the year 2000, Pulmonary and Critical Care physicians ventilated the vast majority of patients with tidal volumes of 700-900ml’s. This was the standard of care at the time and it was not until the ARDS Network trial, published in the New England Journal of Medicine in 2000, that this shifted. We all learned from this study that larger tidal volume use was associated with excess mortality compared to smaller tidal volumes and this was due to ventilator-induced lung injury. While the medical community gradually came to understand this and changed best practice to the use of smaller tidal volumes, there were CRITICAL aspects of this trial that physicians did not understand then, and still do not appreciate today. Understanding the details of the methods applied in this study are of paramount importance if we are to save as many lives as possible.
Over the years, I have treated many patients with ARDS. My experience in the early years was like that of all other Pulmonologists. These patients would frequently die, but if they did not die soon, they would often languish on ventilators for 6 weeks to three months or longer. We never really knew who was going to survive, but back then, only about 40% did. These were the days when we used larger tidal volumes. We did see some improvement when we changed to smaller tidal volumes but it was not as dramatic as one would have hoped. Once I learned more and used the protocol from the landmark study supplemented by medications I added, outcomes changed enormously. During the H1N1 flu epidemic of 2013-2014, I had 6 patients in their 40’s and 50’s who required intubation and mechanical ventilation. All were in ARDS and quite hypoxemic, some requiring PEEP of 20 cm H2O and FIO2 of 100% and barely oxygenating adequately. Applying the new strategy, not only did all of them survive, but they were all liberated from the ventilator in 2 weeks or less. This contrasted with one of my former associates who was a Pulmonologist who had 5 deaths with H1N1 patients with ARDS in the same season and in the same age group. I saw his treatment approach when I would cover for him on weekends and our strategies were obviously very different, accounting for the difference in mortality. The year prior to this, I had also used the same treatment protocol in 4 ARDS patients and, again, each of them survived and got off of the ventilator in 2 weeks or less. So, I had my own series of 10 patients who did remarkably well compared to what had been the usual experience with ARDS. I strongly believe that this is due to an improved treatment strategy that yields better outcomes in ARDS. It is this protocol that I would like to share with you.
The All-Important Plateau Pressure
In the ARDS Network trial, reducing tidal volumes to 6ml’s per kg ideal body weight (IBW) was not all that was done to achieve the 22% drop in mortality. No. The protocol also required that the plateau pressure be 30cm or less. If it was above 30cm while using tidal volumes of 6ml’s per kg IBW, one had to drop the tidal volume lower, such as to 5ml’s per kg IBW or even 4ml’s per kg IBW to achieve the lower plateau pressure. This is absolutely critical to the success of this approach and most ICU’s show little concern for closely monitoring the plateau pressure in ARDS.
Understanding the plateau pressure and how it is measured is important. With the simple ventilators I used during residency, I would measure plateau pressure by occluding the expiratory port of the ventilator, using either my hand or a credit card. On modern ventilators, there is an inspiratory hold button that takes care of this and this is applied for 0.5-2.0 seconds. Plateau pressure cannot be measured accurately if the patient is spontaneously breathing. It can only be measured accurately if there is no respiratory effort on the part of the patient and they are being passively ventilated. Paralysis of the patient is often the best way to achieve this but paralysis is to be avoided beyond 48-72 hours.
Plateau pressure is best explained in terms of a volume-controlled breath such as when the ventilator is set on assist control (AC). The pressure at end inspiration is called the peak inspiratory pressure, the highest pressure reached in the breath cycle. This is also called the trans-respiratory pressure which is the sum of the trans-airway pressure and the transthoracic pressure. The trans-airway pressure is due to flow and resistance, so the peak inspiratory pressure could be elevated due to a change in flow or resistance (such as due to bronchospasm or secretions) and have nothing to do with lung expansion. Transthoracic pressure is composed of trans-alveolar pressure and transmural pressure. Transmural pressure relates to chest wall compliance. What we are really interested in with ARDS is transalveolar pressure as this is a reflection of lung compliance, the determining factor in the generation of lung overdistention and injury. It is plateau pressure that relates to this lung compliance and/or stiffness of the lungs. That’s what we want to measure. It is measured by the cessation of air flow at the end of inspiration. With no air flow, there is no contribution of resistance from the airways. However, a noncompliant chest wall (such as with obesity or ascites) could contribute still to this pressure. In the ARDS Network trial, the tidal volume was reduced progressively until the plateau pressure was 30 cm or less. This is an initial goal, but I have found (as others have) that reducing the plateau pressure to 25cm H2O or less really yields an excellent chance of recovery. This may not be feasible initially but it is definitely what you should aim for as soon as possible. Notice that reducing tidal volume is the main way to achieve this, but if the patient is improving, reducing PEEP also contributes to reduced plateau pressure.
So, in addition to measures of oxygenation and ventilation, it is the plateau pressure that lets us know how the lungs are doing!!
Initial Ventilator Settings
I strongly recommend that you use volume control such as assist control (AC) when setting up the ventilator. Not that you couldn’t set this up with pressure control but monitoring plateau pressure is harder in pressure control and you may have to use the peak inspiratory pressure for your plateau pressure. I would not use any sort of adaptive pressure control such as PRVC (Servo), VC+ (Puritan Bennett), or auto flow (Hamilton). These will just muddy the waters and not get you the results you want. Don’t let your respiratory therapists try to tell you that they prefer these adaptive pressure control settings! Some patients are more comfortable with these settings but adaptive pressure control is as much about marketing as it is physiology. All of the excellent results I have gotten in ARDS are based on volume control (AC) and the ARDS Network trial was done using volume control. If someone wants to do an ARDS trial with PRVC, VC+, or auto flow, that’s fine. Let them figure out how best to do this. I strongly encourage you to use volume control for ARDS and I would NEVER use PRVC, VC+, auto flow or any other type of adaptive pressure control so popular in today’s marketing of ventilators.
Setting Tidal Volume
In deciding on the tidal volume to be set after intubation, the first thing you need to know is the patient’s height. Ideally, this information should be obtained from the patient on admission. If that has not happened and the patient cannot tell you, one can ask family, look on the patient’s driver license, or guesstimate. It is important to use the ideal body weight formulas to calculate the appropriate tidal volume and not just guess at it. Guessing yields less than optimal results. Giving a 350ml tidal volume to a 5’4” male may be fine, but the same 350ml tidal volume is excessive when given to a 5’ tall woman. Pulmonologists would be well-advised to use the ideal body weight (IBW) formulas to calculate the appropriate tidal volumes.
Males IBW (kg) = 50 + 2.3 (height in inches – 60).
Females IBW (kg) = 45.5 + 2.3 (height in inches – 60).
Once you have calculated the ideal body weight, you use that in all calculations of tidal volume. As per the ARDS Net trial, initial tidal volume is set at 8ml’s per kg IBW. It is reduced to 7ml’s per kg IBW, followed by a further reduction in the tidal volume to 6ml’s per kg IBW. This reduction in the tidal volume to 6ml’s per kg IBW is carried out within the first 4 hours after intubation. Once the tidal volume is at 6ml’s per kg IBW, if the plateau pressure is still greater than 30cm H2O, reduce the tidal volume to 5ml’s per kg IBW. If the plateau pressure remains >30 cm H2O, the tidal volume is reduced to 4 ml’s per kg IBW. Of course, ABG’s and pulse oximetry continue to be monitored. Some researchers have even used lower tidal volumes with good results.
Since the tidal volumes will be lower, you will need a higher respiratory rate than normal to achieve a given minute ventilation. Using a respiratory rate of 28 or 32 is not a problem and I have sometimes had to use respiratory rates of 35 to 40. Of course, during the low tidal volume ventilation, permissive hypercapnia means allowing the pCO2 to rise and the pH to fall. The increased pCO2 is partially offset by increasing the respiratory rate. The pH was allowed to drop as low as 7.15 in the ARDS Net trial and no adverse effects were noted. There should be no hesitation about letting the pH drop this low and even a little lower. It is important to remember that in the ARDS Net trial, the more normal the patient’s ABG, the HIGHER the mortality. We are not aiming for normal ABG’s. Our goal is to reduce ventilator-induced lung injury and reduce mortality. This should be discussed with the ICU nurses and respiratory therapists as this requires a shift in mindset.
Setting the FIO2 and level of PEEP needs to be individualized but I have just a couple of comments about this. Having pO2’s in the mid-50’s or a little lower and O2 saturations in the mid-upper 80’s may need to be tolerated. Higher levels of PEEP are often tolerated as long as the tidal volumes are really reduced.
If you are confident that the patient is in ARDS, do not use noninvasive ventilation. In fact, I would go so far as to say that it is probably contraindicated in the treatment of ARDS. I have worked at multiple hospitals where I have seen BIPAP initiated on ARDS patients in an effort to avoid intubation. I have consistently seen poor results if the BIPAP was maintained for any significant length of time. I know of three patients in their 40’s and 50’s who were placed on BIPAP for 2 or more weeks. Despite subsequent intubation, all of them went on to die of respiratory failure. This occurred as a result of BIPAP-induced lung injury. It is difficult to control tidal volumes when using BIPAP and these patients were receiving tidal volumes of 600ml’s or more. This led to worsening of acute lung injury and irreversible respiratory failure and death. This has not been discussed much in the medical literature but I am convinced it is a very real phenomena.
Medications Used in ARDS
The use of corticosteroids in ARDS is controversial and it has waxed and waned over the years. I have seen a couple of patients with very severe hypercapnia with persistent pCO2’s of greater than 100 respond dramatically to steroids. It is my personal bias, however, that I do not usually use steroids in ARDS. The side effects I have seen include muscle weakness, agitation/steroid psychosis, hyperglycemia, increased catabolism, increased BUN, increased WBC clouding the picture, blunting of the febrile response, poor wound healing, and possible immunosuppression. Even so, a decision for or against steroid use can be made on an individual basis.
Neuromuscular blocking agents have often been reserved as a salvage maneuver for severe ARDS, but there is evidence in the literature of a beneficial effect of the early use of a paralytic agent. Advantages of using a paralytic agent in the first few days include being able to obtain an accurate measure of plateau pressure, improvement in hypoxemia, improvement in ventilator-patient synchrony, and decreased incidence of barotrauma. My experience with severe ARDS is that neuromuscular blocking agents are helpful for the first few days. I would avoid its use beyond 48-72 hours as severe muscle weakness (especially if given with steroids) can result and persist for a long, long time. A paralytic agent may not be needed in less severe ARDS, and a short acting agent such as Succinylcholine could be used intermittently to measure plateau pressure.
I have found diuresis to be a useful and effective strategy in the treatment of ARDS. There is evidence that pulmonary edema due to increased permeability, as in ARDS, does worsen as intravascular hydrostatic pressure rises. So, “keeping the lungs dry” would seem an appropriate strategy as long as hypotension is not an issue. I have repeatedly seen that liters of fluid removal often correlated with remarkable improvement, even in those with no sign of prior cardiac dysfunction.
Of course, prone positioning and ECMO are salvage strategies that can be considered as well.
Know the patient’s height prior to intubation
Place on AC settings with higher than normal respiratory rate
Using ideal body weight equations, calculate tidal volume for 8ml per kg IBW and start on this after intubation
Males IBW (kg) = 50 + 2.3 (height in inches – 60)
Females IBW (kg) = 45.5 + 2.3 (height in inches – 60)
Reduce tidal volume to 7ml per kg IBW and later 6ml per kg IBW.
Monitor plateau pressure and the goal is 30cm H2O or less initially
If plateau pressure is above 30cm H2O while on tidal volume of 6ml per kg IBW, reduce tidal volume to 5 ml per kg IBW. If still above 30cm H2O, reduce to 4 ml per kg IBW
Seriously consider paralytic agent but avoid using it for more than 48-72 hours
Remember that in the ARDS Net Trial, the more normal the ABG, the HIGHER the mortality. Do not hesitate to allow the pH to drop as low as 7.15 and even a little lower.
Bicarbonate infusions to raise low pH are unnecessary.
If BP is adequate, use diuretic therapy
Keep trying to reduce plateau pressure with a goal of 25 cm H2O or less. The lower the plateau pressure, the better.
The Acute Respiratory Distress Syndrome Network. Ventilation with Lower Tidal Volumes as Compared with Traditional Tidal Volumes for Acute Lung Injury and the Acute Respiratory Distress Syndrome.
N Engl J Med 2000; 342:1301-1308; May 4, 2000.
Papazian L, Forel JM, Gacoulin A et al. Neuromuscular Blockers in Early Acute Respiratory Distress Syndrome. N Engl J Med 2010; 363: 1107-1116; September 16, 2010.
Yegneswaran B, Murugan R. Neuromuscular Blockers and ARDS: Thou shalt not breathe, move, or die! Critical Care 2011, 15:311.
The National Heart, Lung, and Blood Institute ARDS Clinical Trials Network. Comparison of Two Fluid-Management Strategies in Acute Lung Injury. N Engl J Med 2006; 354: 2564-75.