Approaches to Clinical Management for Patients with Ebola Treated in U.S. Hospitals

Coordinator:
Welcome everyone and thank you for standing by. All participants have been placed on a listen-only mode until the question and answer session. To ask a question please press Star followed by 1 on your touch-tone phone. Today’s conference is being recorded. If you have any objections please disconnect at this time. I would now like to turn the conference over to Loretta Jackson-Brown. You may begin.

Loretta Jackson-Brown:
Thank you Wendy. Good afternoon. I’m Loretta Jackson-Brown and I’m representing the Clinician Outreach and Communication Activity, COCA, with the Emergency Communications System at the Centers for Disease Control and Prevention. I’m delighted to welcome you to today’s COCA call, Approaches to Clinical Management for Patients with Ebola Treated in US Hospitals.

There is no continuing education or slides provided for this call. Additional resources for clinicians are available on the COCA Web page at emergency.cdc.gov/coca. Look under the October 20 call Web page.

Our first presenter today is Dr. Tim Uyeki. Dr. Uyeki is the Clinical Team Lead for the Ebola response at CDC. The next presenter is Dr. Diana Florescu. Dr. Florescu is an infectious disease specialist of the Section on Infectious Diseases at the University of Nebraska Medical Center. The last presenter today is Dr. Marshall Lyon III. Dr. Lyon is an Associate Professor in the Division of Infectious Diseases at Emory University School of Medicine.

In addition to today’s presenters, CDC subject matter experts, additional colleagues from the University of Nebraska Medical Center and Emory University School of Medicine will be available to answer questions during the Q&A portion of today’s call.

At the end of the presentation, you will have an opportunity to ask the presenters questions. On the phone dialing Star 1 will put you in the queue for questions. Questions will be limited to clinicians who would like information on clinical management or clinical guidance for patients with Ebola. For those who have media questions please contact CDC Media Relations at 404-639-3286 or send an email to media@cdc.gov. At this time, please welcome Dr. Tim Uyeki.

Dr. Tim Uyeki:
Thanks Loretta and thanks for our participants today. The purpose of today’s call is to really inform US clinicians about clinical management issues for patients with Ebola virus disease.

We will not be discussing infection control. We will not be discussing triage questions for suspected cases, persons under investigation. We’re really going to focus on clinical management issues for patients with confirmed Ebola virus disease in the United States.

To date, as most people know, there have been eight patients with Ebola virus disease who have been cared for at hospitals in the United States, to date. All of these eight individual patients are adults. Of these eight, five were medically evacuated from West Africa. In addition, there was one case that was imported and identified in the US and two secondary cases that were attributed to exposure to that imported case.

Of these eight individuals, four have been discharged from hospital, one has died and three are currently hospitalized. I would like to note that the purpose of this call is to share information for US clinicians. It is not for - it is not intended for the general US public, it is not intended for the US media and press.

We are trying to avoid discussion of patient identifiers. And we would appreciate not focusing on individual patients here. We’re trying to address general issues related to patients with Ebola virus disease in the US.

So I’m going to briefly discuss some of the clinical features and then turn it over to our colleagues from the University of Nebraska Medical Center as well as Emory University Hospital.

So patients with Ebola virus disease typically present with a nonspecific febrile illness that lasts for about three to four days. And during this period they may have fever, chills, myalgias, malaise, weakness which may be substantial weakness, and anorexia.

These are all very, very nonspecific symptoms - signs and symptoms. And after about three to four days, a number of patients may experience gastrointestinal manifestations. This may be reflected by vomiting and in particular diarrhea as well as abdominal pain.

In addition, around this period of time, somewhere around days four to six to seven, there may also be the development of a rash. In other words, the gastrointestinal manifestations and the rash are not really present in the first few days of the illness. There’s a progression of signs and symptoms.

There are - the diarrhea may be very profuse. And I think we’ll hear about that from our clinical colleagues.

There are many other kinds of complications that can develop as a result of Ebola virus disease. And I’m not going to mention those right now because I think it’s best to proceed to hear from our clinical colleagues about some of the signs and symptoms and issues about the clinical course and management from them.

So at this time I’d like to turn the presentation over to Dr. Diana Florescu of the University of Nebraska Medical Center. Diana?

Dr. Diana Florescu:
Thank you. Our patients were two male without significant past medical history who tested positive for Ebola virus and were transferred to our facility for treatment.

For simplicity, the timeline of the clinical presentation starts with the date of diagnosis and clinical symptoms, not with the date of admission to our hospital.

Both patients presented initially with fever and myalgia. Subsequently they developed decreased appetite and severe nausea, day 2 and day 4, vomiting, day 4 and day 6, and diarrhea, day 2 and day 4.

Both patients vomited once or twice per day. And diarrhea was watery, non-bloody and increased in frequency during the days prior to admission to our hospital.

Patients also complained of malaise, fatigue and profound generalized weakness that started for one patient day 4 and the other one, day 6. Both patients developed a generalized rash, day 5, days 6 of the illness. And one of the patients described the rash as being pruritic.

On admission to our hospital, patients had stable blood pressure. They were not hypertensive. They were febrile. The temp was as high as 39 and 39.5 Celsius. That would be 102 to 103 Fahrenheit. And they had relative bradycardia. They were not hypoxic.

On physical exam, we noticed conjunctivitis, on both patients, bilateral conjunctivitis, and glossitis. One patient had more severe glossitis.

And we noticed the rash on both patients that was generalized macularpapular rash.

One patient had confusion and it was unclear if the confusion was due to dehydration, or to viral infection or to the medication he received during transportation. He was agitated during transportation and he received Ativan, Haldol and Dilaudid.

On admission the laboratory data was significant for hyponatremia in one patient and both patients had hypomagnesemia and hypokalemia; these were expected electrolyte abnormalities in a patient who is vomiting and had diarrhea.

But our patients did not have acidosis or renal failure. Both had hypoalbuminemia and abnormal liver function there.

AST and ALT were (mildly) elevated with an AST higher than ALT. Alkaline phosphatase – Alk Phos was mildly elevated. Bilirubin was normal.

One patient had normal white count, one had mild leukocytosis. And both had thrombocytopenia.

One patient was anemic on presentation. The other one did not have anemia. Both patients had coagulation abnormalities high INRs, PT and PTT.

During hospitalization, the symptoms continued to persist but first symptoms to resolve was vomiting, after two and respectively eight days vomiting resolved.

Diarrhea resolved after six to eight days on both patients. And after the diarrhea resolved patients did not have bowel movement for two, three days. And when they started having bowel movement again, they continued to have loose bowel - loose stools.

Nausea was more persistent, required medication and resolved after 13, 14 days, and once that nausea resolved the appetite returned.

Fever was persistent, 11 days one patient 17 days the other patient. And also myalgia was persistent 16 days - 14, 16 days.

The most persistent symptom actually was the generalized weakness, up to discharge for our patients.

At day nine of the illness, both patients started to develop cough. And this was corresponding with chest x-ray finding of lung infiltrates. And these infiltrates resolved after four or five days and cough also resolved.

One patient had sore throat, day 6 of illness. And this sore throat persisted for seven days. Headache, one of the patients days six of illness for eight - persisted for eight days.

The rash that I mentioned persisted for three, and seven days the other patient. And when rash resolved, one patient started having petechiae and this petechiae resolved after eight days. Another patient, the other patient developed bruises on the arms on the sites where we had the blood pressure cuff. And the bruises persisted for ten days.

We have some neurological findings in our patients: One of the patients complained of paresthesia on fingers but these were transient, only for one day; Tremor of the hands, that was a mild tremor, persistent for five days; Delirium for - one of the patients had delirium day ten of the illness and was present for two days; And insomnia started when delirium resolved and was controlled with medication.

One patient had orthostatic hypotension late in the course of the disease, day 18 of the illness. And we performed ACDH stimulation test and was - came back normal.

Regarding laboratory - actually I should mention the stool output. The stool output for our patients was as high as 3400 mL and tapered down very fast during the first day -days of hospitalization.

And our patients did not require a rectal tube. They could use the bedside commode. The emesis output was as high as 1400 mLs and we were able to maintain a good urine output throughout the hospitalization and to balance the fluid status, ins and outs.

Regarding the laboratory data patients had hypokalemia and hypomagnesemia while they had the diarrhea, and then these resolved.

They - one patient was persistently hyponatremic. Now none of them had acidosis or (renal failure) (unintelligible).

Albumin reached the nadir day 10 and day 16 of the illness, probably correlating with protein wasting enteropathy, and then started increasing for one patient day 13 and the other one day 22.

AST for both patients remained much higher, three, four times higher than ALT, peaked at day nine of illness for both patients and normalized a day 15 and day 22.

Alkaline phosphatase – Alk Phos did not increased dramatically, actually plateau and started decreasing when we stopped the TPN. And perhaps TPN had some contribution in this persistent - persistently elevated alkaline phosphatase – Alk Phos.

I mentioned that renal function was normal on admission and we didn’t have any renal failure in our patients.

White count climbed after admission and both patients had persistent leukocytosis, that we attributed to infection with Ebola virus.

One patient was anemic on admission. The second patient actually dropped hemoglobin, hematocrit on the day 8 of illness. And they both remained anemic throughout their hospitalization.

Thrombocytopenia reached the nadir of around day 6, 7 and platelets turned to normal value around day 10 to 12.

Coagulation factors INR and PT were the first to normalize day 7 and day 10. And PTT was the last value to come back to normal around day 12, day 13.

Regarding virology results, the - one of the patients became viral load undetectable day 22 of the illness and the other patient almost undetectable day 18 of the clinical illness.

Patients received treatment with the investigational drugs with Tekmira - TKM100802 and Brincidofovir. And both patients received Convalescent serum (should say plasma). And the main treatment was the supportive therapy.

Fluids, we used lactated ringers and sodium chloride.

For nutrition we administered TPM and Intralipid 20%. We repleated the electrolytes, with potassium chloride and magnesium sulfate.

For symptoms: fever was controlled with Tylenol, nausea with metoclopramide, ondansetron or scopolamine patch. Diarrhea: for diarrhea we used Imodium. For cough we used dextromethorphan.

I’m not sure if Dr. Smith would like to add anything?

Dr. Phil Smith:
I just - a couple of comments. That’s a nice presentation.

All these people presented with, as Dr. Uyeki mentioned, marked early toxicity, high fever. It’s a striking illness in its early phases.

In our patients the - perhaps the more striking laboratory abnormalities were thrombocytopenia and markedly elevated liver function tests.

They all seem to have an early dehydration phase followed by the - a later cough and a mild pulmonary edema phase.

And in one case this was accompanied by soft tissue edema. So this rather leak capillaries due to a cytokine reaction or over rehydration we’re not certain.

Add lastly we were struck by these even people who are young and fit have a very prolonged weakness and slow convalescence. So it’s an illness that tends to have a significant effect on a person’s physiologic functioning.

So I guess that’s all we have in Nebraska here. I’ll turn it back to Tim.

Dr. Tim Uyeki:
Thanks very much Dr. Florescu and Dr. Phil Smith. I’d just like you both to just address one question before we move on to our Emory colleagues. And that is could you just comment on the use of antibiotics in your patients and when in the clinical course?

Dr. Phil Smith:
Yes. One patient came to us with and had received a third generation Cephalosporin in Africa and arrived with what we think is a drug rash. Both of them also had sort of a blotchy macularpapular rash. We assume was due to the Ebola virus.

Our - and I know some people have a policy of empiric broad-spectrum antibiotics because of possible bowel - loss of bowel integrity due to the diarrhea.

We have - all our patients were febrile. We cultured and watched in both cases without broad spectrum antibiotics. And in neither case did we require them later on and were not able to detect a bacteremia. The fever came down slowly but steadily with either the natural history of the disease or due to the antivirals. We’re not sure.

I suppose if we had started broad spectrum antibiotics we would be thinking that we had something to do with the defervesence but that - we’ll leave that up to clinical judgment I guess.

Dr. Tim Uyeki:
Thank you very much Dr. Smith. Now I’d like to turn the presentation over to our Emory colleagues and Dr. Marshall Lyon will provide a summary of their four patients. Dr. Lyon?

Dr. Marshall Lyon III:
Thank you Dr. Uyeki. This is Marshall Lyon at Emory University. So we treated four adult patients here at our institution. And they have ranged in age from the late 20s to the late 50s.

Just to echo sort of what was announced earlier in terms of the typical course of Ebola after the initial three to four days of malaise and fever there is about a five to six day window of the gastroenteritis phase.

Most of our patients came to us at just the beginning of the gastroenteritis phase or during the gastroenteritis phase.

So we had within that window the gastroenteritis there was about one to three days of vomiting. The diarrhea lasts longer than the vomiting.

The vomiting certainly complicates trying to orally rehydrate or resuscitate any of these patients.

We saw stool outputs which ranged from 4 to 12 liters per day. We did see some oliguria and even anuria in one patient which would be talked about a little bit later.

So also during the time of the gastroenteritis phase this is when you see clinical dehydration and hypovolemia and marked electrolyte abnormalities.

So much like our colleagues in Nebraska noted we noted that we had some hypokalemia. And this was associated with some cardiac arrhythmias in patients. These were both ventricular and atrial arrhythmias.

We also noted hypoalbuminemia which had an associated hypocalcemia.

I will note that the calcium was out of proportion was lower out of proportion to what you would expect for the amount of hypoalbuminemia.

So the - so, you know, our resuscitation in terms of volume and electrolytes focused primarily on calcium and potassium.

We didn’t have the ability in our unit to measure magnesium because we’re using point of care instrumentation. We assume that there was hypomagnesemia and so we did supplements with magnesium as well.

So towards the end of the gastroenteritis phase which is now somewhere around day ten of illness, you start to see sort of a vascular leak/sepsis phase that some patients go into.

This was noted also in the Nebraska patient. So you see this what we found most commonly in our patients was subcutaneous edema.

We did note that there was a small pleural effusion in one of our patients. And so this starts to create some problems with volume resuscitation because if you’re overaggressive with volume repletion then you can drive the (subcutaneous) edema and theoretically a pleural effusion as well.

In terms of the clinical course keeping with this as I mentioned one of our patients developed anuria. And this did progress to acute renal failure and a syndrome that was consistent with ATN.

We did support our patient with hemodialysis during that timeframe. The patient also developed a hypoxic respiratory failure in that time and did require intubation and mechanical ventilation for a period of about ten days.

We do have a critical care colleague who is on the line and will discuss more about the critical care aspects of this patient’s course.

Most patients once they sort of the get if they don’t develop a frank sepsis -- and this is a viral sepsis not a bacterial sepsis although secondary bacterial infections are certainly possible -- if they don’t develop that septic phase then generally once the GI problems end then they are on the road to recovery.

About one to two days after the resolution of the diarrhea this is when you start to see it the vessels begin to not leak so much and fluid can actually be reabsorbed in a rather rapid fashion.

Two of our four patients when they hit this phase actually had a 10 kilo weight loss overnight with a concomitant 10 liter volume of output in the urine. It was rather dramatic how these people go from puffy to normal in the space of a 24-hour period.

We too had neurologic complications in our patients. We had one patient who developed a peripheral neuropathy in both feet.

This responded nicely to narcotics for acute pain relief and ultimately to gabapentin at about 300 milligrams TID provided nice relief.

Another patient had a similar to the Nebraska case tingling of the bilateral upper extremities. Interestingly this patient also had some delirium and had amnesia for a large part of the illness.

In terms of our laboratory abnormalities I’ve already mentioned the electrolyte abnormalities that we saw during the gastroenteritis phase.

We also saw much has been commented from Nebraska that hepatitis, the chemical hepatitis. This was primarily in the transaminases with the AST being markedly more elevated than the ALT.

We did see some element of hepatitis in all four of the patients that we have treated. Two of the patients actually had a severe course of transaminitis and the other two actually had mild transaminitis.

We did not see hyperbilirubinemia and we did see some elevated alkaline phosphatases. But in general they were not too bad although one patient probably had a fairly marked elevation in alkaline phosphatase which we attributed to a persistent and repletion refractory hypocalcemia.

In terms of the microbiology we followed PCRs. For most of our patients the PCRs remain positive but no later than day 28 of illness they - you usually see resolution of the blood PCR between three and four weeks of illness.

We noted that the decline in the PCR corresponds to two things. It roughly corresponds to the start of the improvement or the resolution of the symptoms and also with a surge in the IgM and IgG specific to Ebola.

We used in terms of volume resuscitation because there’s is a lot of IV fluids that were used here and we did place central lines in three of our four patients had central lines.

We used initially for acute resuscitation for hypotension normal saline. We tried to use lactated ringers.

And Dr. Connor may comment on trying to avoid chloride containing compounds because of the association with renal failure in critically ill patients. So plasma light might be a nice alternative to normal saline.

In terms of coagulopathy we actually did not see coagulopathy in our patients. We were following INRs. The highest INR we ever had was 1.7 which did not correlate with any clinical bleeding.

We did have clinical or signs of hemorrhage or bleeding in some of our patients. This was mainly seen as oozing around IV sites.

We did see a little bit of gum bleeding in patients and then also a little bit of nose bleeding. All of this was relatively minor with no significant drops in hematocrit.

Likewise we did see thrombocytopenia in all of our patients with the lowest getting down to a platelet count of 24,000. Responded nicely to a single platelet transfusion. And then spontaneously after that transfusion began to increase back to the normal range.

Like our colleagues in Nebraska we did use experimental therapy. Two of our patients received ZMapp which is a three-monoclonal antibodies to three different epitopes of a surface protein of the Ebola virus.

It is a mouse-human hybrid. We used convalescent sera in two of our patients. And then we used a product that is called TKM Ebola in two of our patients.

With the TKM Ebola product we did notice some fever and some hyportension which was felt to be possibly related to the medication administration.

We did not necessarily note those issues with the convalescent sera. With the first doses of ZMapp in and two of our patients there were some mild allergy type reactions which responded nicely to diphenhydramine in both cases.

Both of those patients subsequently tolerated their second and third doses of the ZMapp product without much problem.

In terms of the duration of hospitalization most of our patients left the hospital by day 28 of their illness. The one patient that was critically ill did remain in the hospital for almost one month which would have been about 32 days of illness.

Like Dr. Smith said our patients have a fatigue which is associated with this. And probably recovery from this fatigue lasts longer than other illnesses including say influenza.

It seems to be somewhat variable and also is proportionate to how hard the individual tries to be active after they’ve begun to recover from their illness.

We used as our discharge criteria PCR of the blood. In conjunction with our public health partners we decided that our patients should have at least two negative PCRs from the blood before they would be allowed to be discharged.

Of course they weren’t discharged unless they were clinically ready to be discharged as well.

In two patients we did notice that the virus remained in the urine after it had cleared from the blood. In one of these patients it was about six or seven days after the blood had cleared and the other two it was about half this amount of time.

And we are also finding when we look much like has been demonstrated before that the virus can be detectable in the semen and it can persist for quite some time in previous studies up to 70 days.

Obviously this has an impact for discharge counseling of patients, male patients. If they’re going to be sexually active then need to use some sort of barrier precaution.

And I think with that I will turn this back over to Dr. Uyeki.

Dr. Tim Uyeki:
Thanks Dr. Lyon. And I think at this point I’d like to invite Dr. Michael Connor who’s an intensivist, a critical care specialist at Emory as well as a nephrologist to comment about the critical illness in one of the Ebola virus disease patients and then followed by some comments by Dr. Harold Franch of Emory University Hospital. And Dr. Franch is a nephrologist. So I wonder if both Dr. Connor and Dr. Franch can comment about the critically ill patient. Dr. Connor?

Dr. Michael Connor:
Hi Tim. Thank you very much. This is Michael Connor from Emory. And as Dr. Uyeki mentioned I am dual trained in critical care and nephrology. So as has been alluded to by Dr. Lyon we did experience one of our four patients progressing to critical illness with multi-organ failure symptoms.

And as has been sort of discussed earlier in this call, this progression of illness seemed to develop as the patient recovered from the gastroenteritis and diarrheal phases of his illness.

The initial presentation of this was a rather rapid development of acute kidney injury and impairment in small solute excretion with BUN and creatinine increasing quite rapidly.

And at the same time progression of hypoxemia increasing oxygen requirements, respiratory distress, and the development of a diffuse interstitial infiltrate consistent with an acute lung injury ARDS physiology.

Given that we were unsuccessful at attempting to augment urine output with diuresis in light of the acute kidney injury, we proceeded to endotracheal intubation and initiation of mechanical ventilation and continuous renal replacement therapy for this patient.

The phenotype that this patient displayed I think is one that is increasingly being seen globally in a subset of the evacuated Ebola patients to the developed world.

There is a proportion of them who about the same time and illness as the diarrheal symptoms improved have developed this worsening hypoxica respiratory failure and acute kidney injury.

It should be noted that our patient also was suffering from a significant degree of encephalopathy and delirium. And this complicated our ability to sedate him requiring rather extensive amounts of sedation with both Fentanyl for analgesia as well as sedatives with propofol mostly.

We did not develop any significant amounts of hemodynamic instability. There was low dose vasopressor requirements that were needed during the critical phases of his care largely related to our attempts to remove volume and ongoing needs for copious and generous sedation dosing.

We did not develop any significant cardiogenic impairments or obvious impairments in cardiac output. And lactic acidosis was rather minimal.

The patient did progress to sort of require higher levels of mechanical ventilation support with elevated levels of PEEP and FI02. However, over the course of about one to two days this stabilized and he was able to have lower amounts of FI02.

And but we had trouble weaning from the ventilator for several days despite an improvement in the chest x-ray.

And we only were able to make significant improvements in oxygenation where we could minimize then settings to minimal needs after the viral load started to improve.

We did use broad-spectrum antibiotics at this time. I know that question was asked before. But our patient had persistent leukocytosis and in light of the deterioration in the clinical course we were uncertain as to whether or not a secondary infection which would be a common cause of the decline in general critical illness in general might have contributed to the change in clinical course. And as such we maintain him on broad spectrum antibiotics for four to five days.

Dr. Lyon might be able to comment on the duration of that a little bit later.

One of the aspects of the critical illness that we certainly wanted to convey in this particular case was that there was a lot of careful consideration regarding organ support and life-support therapies as we recognize that providing these therapies in a bio-containment high isolation area might introduce potential complications.

And so we made extensive preparations like having re-intubation medications immediately available at the bedside.

Dr. Franch will talk about the dialysis and how that was maintained and the considerations that were made as we were initiating dialysis.

Dr. Lyon mentioned that we’ve migrated our thought process in the volume resuscitation phase during the gastroenteritis and dehydration phase to one that’s focused more on balance crystalloids with lactated ringers and (plasmalyte A).

As many on the phone call listening on the phone call may be aware there’s been an evolution in literature in the critical care arena over the course of the last three to four years which is increasingly suggesting that hyperchloremic solutions such as 0.9% normal saline might contribute to organ failures, especially renal failures and that there is an increasing sense that both mortality and potentially renal failure outcomes might be improved with resuscitations focused on balance crystalloids.

And so we have begun the process of re-exploring that.

The other aspect of the case that should be noted is that while this patient did have hypervolemia that might have contributed to the pulmonary edema in the ARDS physiology there was not a striking degree of hypervolemia, only reached a peak of about 7% above his admission bodyweight.

And this has been noted I think globally as well that there seems to be hypoxia and sort of pulmonary edema that develops out of proportion to massive volume overload.

In other words patients are not massively volume overloaded when they are developing the hypoxia.

But in light of that we are reconsidering a process of focusing our resuscitation to maintain euvolemia as opposed to potentially exacerbating hypervolemia.

So with that let me take a pause and let me ask if Dr. Franch has joined the phone and if so if he would like to discuss a bit about the dialysis in this situation?

Dr. Harold Franch:
Yes. This is Dr. Harold Franch, Hal Franch, Emory Nephrology. The, you know, the nephrology issues, you know, the patient was already hyponatremic which indicates a lack of profusion of the aortic arch baroreceptors leading to the release of ADH. So the patient had evidence of functional volume depletion at the time that the creatinine began to rise.

However, the patient was not volume responsive in their creatinine. And the infectious disease doctor was able to do a microscopic urinalysis and noted many muddy brown casts indicating acute tubular necrosis.

Acute tubular necrosis has been noted in the CDC autopsy series of filovirus infected patients from the 90s up to 2007 that was recently published that in the patients who died this was a very common finding.

The rise in the serum creatinine is also noted to be a negative prognostic factor in some of the African studies where laboratories are available.

The patient was originally responsive to diuretics. And we were able to maintain the patient with high dose of furosemide and thiazide in combination.

But eventually as Michael commented we were no longer able to control the patient’s volume status with diuretics and CRRT was begun.

In terms of the choice CRRT it was a matter of putting a few patient - I mean as few personnel in the patient’s room as possible.

Our ICU nurses are cross-trained to run our continuous dialysis machines and this allowed no additional personnel to have to enter the room or be exposed.

A second advantage was that the CRRT machine runs for 72 hours at a time especially when you use regional citrate anticoagulation.

We did not use heparin because at that time the patient was oozing from every line placement site indicating a coagulopathy. And regional citrate made sense.

The negative of the renal citrate was that it required additional laboratory testing which included the checking the ionized calcium every six hours.

The third advantage of CRRT was that there was decreased effluent, you know, the spent dialysate and fluid removed from the patient.

While this material should be sterile given the composition of the dialysis membrane our health department required that we treat this before we disposed of it.

The major risk of CRRT in the isolation environment was the line placement itself. And we followed applicable KDIGO guidelines for the best practices in placement of a right IJ catheter.

This catheter functioned well. Dressing changes were a problem with the larger line with blood loss. But other than that the CRRT procedure itself did not increase blood exposure to the nurses to a great extent.

The patient’s clinical course once they - at first the patient was being hypoventilated for an ARDS type protocol on the ventilator. So we matched that by making the patient somewhat alkalotic metabolically.

Then once the patient stabilized we aggressively pursued volume removal. The patient lost somewhere around 20% of bodyweight in fluid during that aggressive volume removal program.

We then watched, you know, switch to an intermittent hemodialysis strategy as the patient became extubated in order for him to be able to move around and start some early rehabilitation activities. The intermittent dialysis was done with the same machine and once again was successful.

Twenty-four days after initiation of dialysis the patient showed evidence of recovering function based on decreasing CRRT dosage required to maintain his labs. And dialysis was stopped.

He’s shown steady improvement in his function and was at an estimated GFR of approximately 33 at the time of discharge. And I think I’ll turn it back to Tim now.

Dr. Tim Uyeki:
Thank you very much Dr. Franch. And also, thanks to Dr. Connor for those comments and background about the critical illness in one of their patients and the management.

And I think what you’ve heard is a real range of clinical presentations and severity of illness from moderate to critical illness with a really wonderful result in the patient who actually has recovered from both respiratory and renal failure with ability to be discharged.

And overall what you’ve heard in a number of these patients is sort of a consistent story of intravascular volume depletion and dehydration and the very important issue of close supportive care, aggressive supportive care, particularly during the diarrheal phase with aggressive intravenous fluid hydration and replacement of electrolytes, namely replacement of potassium as well as calcium but then also replacement of magnesium and also addressing the sodium deficits.

We’ve also heard among the patients to have hypoalbuminemia as well as transaminitis which is varied. And some of these can - elevation of LFTs can be quite high with in general AST markedly elevated versus ALT.

You’ve also heard of a number of complications. One complication that I would just add is that in one of the patients who was discharged at the time still had some visual issues and had presented with unilateral blurred vision about ten days after discharge and was diagnosed with unilateral anterior uveitis which is improving.

That individual and others which you’ve heard about have had some complaints suggesting a peripheral neuropathy and overall generalized weakness.

You’ve also heard about complications such as delirium, confusion. But I think what you’ve heard about in all of these patients is the really critical importance of very good supportive management, close clinical management.

So with that I want to thank the clinician presenters. And at this time I’d like to have them all stick around to be able to answer questions.

Again we want the questions to be focused on clinical management. And I guess while the questions are in the queue I’d like to start out by just asking our Nebraska and Emory colleagues just to comment about the condition at discharge.

Did you find that these patients although they had recovered still had substantial weakness and any other issues at the time of discharge?

So I’ll just start with Dr. Florescu and Dr. Smith at Nebraska. Could you just comment on the overall well-being of the patients at the time of discharge?

Dr. Diana Florescu:
Thank you. So the main complaint at discharge was generalized weakness. That was the most persistent symptom for the first patient and seems to be the persistent symptom on the second patient.

Dr. Tim Uyeki:
Great.

Dr. Diana Florescu:
The rest of the symptoms resolved.

Dr. Tim Uyeki:
Great. And then Dr. Lyon and colleagues could you just comment on sort of any persistent problems at the time of discharge in your patients?

Dr. Marshall Lyon III:
Well fatigue - sorry, this is Marshall Lyon at Emory University. Fatigue was certainly an issue. All of our patients have some element of fatigue and all those that have been discharged complained of tiring easily with just activities of daily living.

In terms of follow-up of the two patients that discharged back in August they still even at one month after discharge complained of some amount of fatigue that had improved but was still present.

So even in my general hospitalized patients I tell them that they should count on about one to two days of recovery outside of the hospital for every day that they spend in the hospital. And I think for Ebola it’s probably two days of recovery for every day in the hospital at least.

The peripheral neuropathy that we saw in one patient had resolved but - at one month post discharge but was still taking Gabapentin at that time. She was given a taper protocol for getting off of that Gabapentin.

And those were probably the biggest things. I think that, you know, I don’t want to say that the patients had confusion but they certainly had difficulties in terms of concentration, had to be reminded about things quite frequently. And I think that that is probably just part and parcel with the fatigue aspect of this illness. Over.

Dr. Tim Uyeki:
Thank you Dr. Lyon. Let me just ask similarly our Nebraska and Emory colleagues just to comment about various procedures.

So at Emory we heard that three of the patients had a central line placed. I wonder if our Nebraska colleagues could comment about the use of central lines as well as a Foley tube and rectal tube. Over, Dr. Florescu, Dr. Smith?

Dr. Phil Smith:
This is Nebraska, Phil Smith. We did not require Foley catheters or rectal tubes in our patients. And our treatment philosophy evolved a bit. In our first patient the vomiting phase was brief and so we tried to get by without - with on oral alimentation. And it was unsuccessful so with our second patient we immediately put in a central line and began TPN day one. And we think that although this is not a controlled study we think that was advisable and we’ve made that our standard approach.

Dr. Tim Uyeki:
Thanks Phil. Dr. Lyon do you want to just comment about Foley and rectal tubes?

Dr. Marshall Lyon III:
Absolutely. We did not use rectal tubes in our first patients. I - this is more of an infection control issue but with the voluminous diarrhea and the rectal urgency that is experienced we did have some incontinence of stool onto the floor of the patient room. And so we have used rectal tubes during that phase in subsequent patients.

Foley catheters we used in three of the patients. One primarily because of that peripheral neuropathy it made it difficult for that individual to stand at the bedside to use a bedside commode.

And others it was for strict INO measurement and also for concerns about the safety, both patient safety getting to and from the bathroom or even to and from a bedside commode.

The central line issue I think it’s important. I know if standard of care to use ultrasound guidance when placing central lines in this day and age.

I would recommend having the most experienced operator do that as with the coagulopathy noted at Nebraska and thrombocytopenia noted in almost all patients.

Obviously you want to have one stick and then success with having a central line placed to minimize possible bleeding complications.

We have been very aggressive with our nutrition. We use oral nutrition as possible. With the vomiting phase obviously that makes it a little bit difficult. But as soon as that resolved even with the addition of anti-medics we were very aggressive at encouraging our patients to intake nutrition.

And in the critically ill patient we moved early to total parenteral nutrition just like the Nebraska folks did. Over.

Loretta Jackson-Brown:
Hey Dr. Uyeki are we ready to open up the lines for the questions? I see we have 30 minutes left and we have instructions that we need to give to listeners.

Dr. Tim Uyeki:
Sure. We’re just about to open it up just in a couple of minutes. We’ll just ask Dr. Lyon and just to comment - did you require special staff to perform the intubation on the critically ill patient?

Dr. Marshall Lyon III:
Yes. We had our anesthesia colleagues come and perform the intubation.

Dr. Tim Uyeki:
Thanks. So this is Tim Uyeki. Before we open it up to questions let me just make a comment about the investigational therapeutics. So what you’ve heard is that a variety of investigational therapies have been administered to the patients with Ebola virus disease. In some of these patients, multiple, in fact most of them, have received multiple investigational therapeutics.

None of these have been administered in a controlled clinical trial. So this is all single patient uncontrolled use. And therefore it is impossible to draw inferences about really the effectiveness and therefore actually either the harm of one particular investigational therapeutic.

I think everyone is looking there for some signal, what is the magic treatment? But I think that for all of these patients as well as (those) outside the US that have received multiple investigational therapeutics in an uncontrolled manner, we really can’t reach any conclusions. And what’s really needed is controlled clinical trials.

So I hope to deflect some questions there about the effectiveness of any one particular investigational therapeutic. And with that I think I’ll open it up to questions.

Loretta Jackson-Brown:
So we will now move to the question and answer portion of today’s call. Questions are limited to clinicians who would like information on clinical management or clinical guidance for patients with Ebola virus disease. For those who have media questions please contact CDC Media Relations at 404-639-3286. Clinicians, when asking a question please state your name and organization. We will now open up the line for the question and answer session.

Coordinator:
Thank you. As a reminder to ask a question over the phone line please press Star 1 on your touch-tone phone. Please ensure your line has been muted and record your first and last name when prompted. You may be announced for your question. If your question has been answered you may press Star 2 to withdraw. The first question is from Jim Allday and please state your organization.

Jim Allday:
Hi. This is Jim Allday with Lifeguard Air Emergency Services in New Mexico. And I really haven’t heard much discussion about the clinical treatment of these patients during air medical transport. I’ve seen the CDC guidelines for air medical transport. But looking at the guidelines and looking at the type of aircraft that the CDC has used to move some these patients around they don’t seem to be functional for the typical air medical aircraft that are used in the United States.

Dr. Tim Uyeki:
I don’t know if Dr. Smith, Dr. Florescu, Dr. Lyon and colleagues at Emory wish to comment about that question?

Dr. Marshall Lyon III:
This is Dr. Marshall Lyon at Emory. I will take a crack at it. Obviously that’s not one of what - that’s not something we do.

You’re correct the aircraft that were used were highly specialized containment aircraft where there essentially was a containment unit in the center of the aircraft. And these were fixed wing aircraft. These were not helicopters.

I don’t think that it would necessarily be easy to retrofit a helicopter to do this. I will tell you that our ground transferred here at Atlanta what they do is they hang drapes along the sides of the ambulance and on the floor so that you essentially cover any exposed surface that you can before they load the patient on.

And they also try to have the patient wrapped in some sort of an isolation blanket if they can. So a water or fluid impermeable drape and then sort of wrap that patient like a burrito style.

I think that method with the drapes on the side of the ambulance works fairly well. And if you were forced to do this for an air ambulance I think that that would be the approach that I would suggest. But I think that if you could do it via ground transport that would be better.

In terms of treatment during the flight it was really just continuing to maintain the hydration status. So if IV access was secure before boarding the fixed wing then those - that was continued.

In one of the patients we received IV access was lost and could not be regained during transport. So we actually - that’s our initial central line placement shortly after arrival. Over.

Jim Allday:
Got you. Thank you very much.

Dr. Tim Uyeki:
Could we have the next question please?

Coordinator:
The next question is from Dr. Rossi Hassad.

Rossi Hassad:
Hi. This is Dr. Rossi Hassad, Epidemiologist Mercy College. Thank you for the value of information. I’m concerned about the lack of essential clearinghouse for information on clinical outcomes.

We have three major sources -- the CDC, the NIH and the WHO. And I don’t think they have all been forthcoming with information about patients. And this is key for effective clinical care.

I mean most recently we have had the World Health Organization claiming that the incubation period for Ebola can exceed 21 days.

And I’m wondering how such information should be factored into clinical management and public health management of our patients or contacts? Thank you.

Dr. Tim Uyeki:
Well I’m not sure we can address that - those questions - those points on this but let me just see if Nebraska or Emory colleagues would like to comment?

Dr. Phil Smith:
This is Phil Smith at Nebraska. It’s a little out of my area but I can just say that every case that I’m aware of has been treated a little bit differently. And there have been shortages of drugs and difficulty in obtaining drugs.

And I think the data is just beginning to accumulate. And I know that there are - I believe the NIH NIAID are looking at the possibility of controlled clinical trials, which is not easy in the setting, in Africa in particular, and even over here; so I don’t know if Tim has anything to add to that?

Dr. Tim Uyeki:
So this is Tim Uyeki from CDC. What I would - the way I would respond is that there are efforts to try to standardize clinical management of Ebola virus diseased patients in Ebola treatment units in West Africa. So those - that guidance is underway in development.

In terms of - and that is in a lower resource type of setting than the kind of supportive and critical care that can be provided in the US or Europe or outside of West Africa.

There are other Ebola virus disease patients that have been medically evacuated to European centers. And a number of those have also required the same kind of clinical management and critical care as the US patients.

So again there’s a range of moderate illness to critical illness. So I think with that we’ll move on to the next question.

Rossi Hassad:
Thank you.

Coordinator:
Thank you. The next question is from Dr. (Sam Hansen).

(Sam Hansen):
Hi. Good afternoon. I’m trying to put together a team of intensivists and nursing staff that I could mobilize in the event that we had an identified case in our small community Hospital.

And I’m wondering what sort of team structures you had put in place to deal with the 24/7 care while minimizing the number of individuals that would be involved or be exposed?

Dr. Tim Uyeki:
Thanks for that question. I’ll let Dr. Smith at Nebraska comment first.

Dr. Phil Smith:
Yes. I guess it depends on your setting. In our unit we had either five or six full FTE RNs, techs and respiratory therapists -- a total of five or six depending on the acuity of the patient that were on duty at any one time.

And our – this is where we were drawing from a pool of about 40 nurses all of whom were volunteers and rotated on a regular basis because of the regular gear.

I think there are - it is possible to have less intensive infection control measures and less intensive nurse to patient ratios and still successfully care for Ebola but that’s the way our unit is set up.

Dr. Tim Uyeki:
Thanks. Phil could I asked Dr. Lyon and others at Emory to comment on that?

Dr. Marshall Lyon III:
Sure. This is Marshall Lyon at Emory. So we had a very similar team. We had a cohort of nurses. Our nurses, we specifically targeted intensive care nurses and emergency room nurses.

And that was primarily because we wanted - we felt like we could potentially have a critically ill patient and we did. And we wanted to have nurses that obviously we could administer critical or ICU level care.

We did not have other ancillary staff in terms of respiratory therapists, phlebotomists, et cetera, just because we wanted to have a limited amount of traffic in and out of our patient care area.

We do have a self-contained point of care lab here within our unit which is our laboratory staff came down and would run whatever needed blood work we had down here on our point of care machines. Technically these could be run by nurses but they’re better served at the patient’s bedside.

In terms of the physician team, I think it is important to have infectious disease physicians especially with a, at least an understanding if not a focus in infection control.

There are a lot of infection control issues that surround this particular disease. And but, you know, I think in terms of physicians outside of ID for less ill patients involving a hospitalist would be a reasonable way to go.

I certainly think that identifying, pardon me, critical care colleagues that can participate in the care of a patient is incredibly important both from fluid balance, respiratory management aspect but also procedural as well.

We had anesthesiologists that we had trained in our safety procedures that were on standby. And we made use of them for placing central lines and then also performing an intubation as well.

And then obviously our nephrologist who is on this conference call was called in to provide assistance.

So I think having various physician partners identified maybe not necessarily part of your initial team but at least people that you can turn to who can provide over the phone or at the door consultations would be very important.

I think in terms of a team that pretty much covers everything that we did. So we - so one thing I will comment in addition to that we’ve been asked how these rooms get cleaned?

And the answer is the nursing and the physician staff do clean the rooms. We don’t involve our environmental services people. We felt that that would just be unfair to them to ask them to clean these potentially highly contagious rooms.

The other thing I’ll comment in terms of providing 24/7 care for any recent grads that are on the phone since the beginning of August through the end of September I violated at least three residency rules every week.

And so, you know, one of the ways to manage this is to actually work a lot of hours. And it takes time. Over.

Dr. Tim Uyeki:
Thank you Dr. Smith and Dr. Lyon. Could we have the next question please?

Coordinator:
The next question is from Dr. Sheena Antonio-Collie. And please state your organization.

Sheena Antonio-Collie:
Hi. This is Dr. Antonio-Collie. I’m calling from Nassau Bahamas Doctors Hospital. I wanted to ask about the point of care testing. With the information we have about limited blood draws was the blood done by finger stick? And how much information were you able to get from those point of care testing? What kind of tests were done? Was it just electrolytes? What type of information were you able to ascertain?

Dr. Tim Uyeki:
Could I have the Nebraska...

Sheena Antonio-Collie:
And what instruments you used?

Dr. Timothy Uyeki:
Thank you. Could I have our Nebraska colleagues respond first?

Dr. Phil Smith:
We used basically an I-Stat for our basic chemistries. There was a point of care lab that we did not have in the beginning but just stood up.

And we also did some - we were able to do some basic things like urine dipstick. We - for other studies like CBC and malaria smears those are transported to our BSL3 laboratory on campus. Over.

Dr. Tim Uyeki:
Dr. Lyon do you want to just comment on your point of care testing and what specific results are available?

Dr. Marshall Lyon III:
Absolutely. And there is no endorsement implied here. We used the Piccolo machine which has various cartridges depending on what sort of quote panel one wishes to obtain.

We used the comprehensive metabolic panel because of the liver involvement. There is a renal panel which gives you some additional data. We also had a small point of care CBC machine as well as a blood gas machine.

I think that, you know, there are advantages and disadvantages to every system. The I-STAT system which was mentioned by Dr. Smith does have quite a bit of flexibility and provides many of the tests that one would want.

You know, we were able to get essentially liver function tests. We had a bedside INR so we were able to monitor that. And with the CBC we of course got platelets, hemoglobin, hematocrit and white count.

We also at the beginning of this purchased a essentially point of care PCR machine which is FDA approved to look at respiratory and gastrointestinal pathogens.

There is an additional panel which is not FDA approved but available to look at bioterrorism agents. This goes by the name of BioFire.

And there are a lot of caveats that go along with that because the bioterrorism panel is not FDA approved. It’s hard to know what the sensitivity of this instrument is.

However it was - we found it to be somewhat useful because we could get rapid results and no criticism of our CDC colleagues. But the tests that were run in their institution would take sometimes about 24 hours to get a result.

Dr. Tim Uyeki:
Thank you. And so I will just comment - this is Tim. I would just comment that both the I-STAT as well as the Piccolo point of care laboratory test platforms have been used in different Ebola treatment units in West Africa. Could we have the next question please?

Coordinator:
The next question is from (Lori Hamburn). And please state your organization.

(Lori Hamburn):
Henry Ford Health System. I’m a nurse and I am a dialysis nurse and I have a few questions for Dr. Franch regarding you said you did CBBH. I was wondering if you used the next stage machine, how long they remained on the continuous treatment before they changed to intermittent, how high was the creatinine level to institute the treatment? And the last but not least you said you treated the dialysate fluid that was spent. Was it just pouring bleach into the waste area that the dialysate fluid was dumped into?

Dr. Tim Uyeki:
Dr. Franch?

Dr. Harold Franch:
Yes. Let me see if I can remember the beginning of that. So we use we had actually had the Prismaflex.

(Lori Hamburn):
Okay.

Dr. Harold Franch:
And that was chosen not because it was necessarily a better machine but because the nurses were more familiar with it.

The advantage of that over the next stage was also because our county health department required the dialysate to be treated. We - it came - it comes in a bag.

(Lori Hamburn):
Right.

Dr. Harold Franch:
But the bags were bulky and hard to handle for the nurses to pour into the toilet. They poured the fluid into the toilet and then added a micro chem product to sterilize it and then flushed it down the toilet.

The - we used initially a CVVHD mode with pure dialysis, low blood flow and the citrates integrated on the Prismaflex machine so it was monitored. You know, it came in and then we used a peripheral IV calcium drip to keep the patient from getting hypocalcemic on the treatment.

We did intermittent of the 24 days probably only - I don’t have it in front of me but probably only the last seven to eight days were intermittent.

(Lori Hamburn):
Okay.

Dr. Harold Franch:
And there we weren’t using a - we weren’t using citrate. And we had it in CVVHDF mode with some pre-filtered dilution to keep the, you know, to keep the filter open during the treatment.

(Lori Hamburn):
Okay.

Dr. Harold Franch:
Let’s see did I - I don’t...

(Lori Hamburn):
Thank you.

Dr. Harold Franch:
All right thank you.

Dr. Tim Uyeki:
Thank you Dr. Franch. Can we have the next question please?

Coordinator:
The next question is from (Kathy Toumei). And please state your organization.

(Kathy Toumei):
Hi. I’m (Kathy Toumei), a registered nurse in Southeastern PA. And I’m going to sit at the local chapter of the Ebola to get our hospital preparedness in effect.

I have kind of a technical question in deciding how the set up rooms. One hospital said the patient was going to go into a room where there was no bathroom facility available which I understand is the CDC recommendation or requirement.

If that is done however and I’d also like to know how you do this. The patients with their in the GI phase with their copious amounts of emesis and diarrhea, one were they able to get out of bed and take care of this themselves? And two if not, did they use a bedside commode, a bedpan, a toilet?

And if that wasn’t a toilet or if - even if it is a toilet is there any concern about - and I think this may have just been briefly answered in the last question about the waste going into the sewer system.

And if it does not go down the toilet how do you treat that waste in a commode, bedpan, et cetera? Thank you.

Dr. Tim Uyeki:
Dr. Smith do you want to just respond from the experience in Nebraska about use of a bedside commode which I believe you said for both patients but also the treatment of the waste?

Dr. Phil Smith:
Yes. We used bedside commodes and that enabled us to measure the output. And I guess we’re fortunate in that both patients were continent and able to use the bedside commode with the assistance of the nurse.

We then poured the secretions into the toilet, added a quaternary ammonium compound in a predetermined ratio and let it sit for 10 minutes and then flushed.

And theoretically the sewer system would handle untreated waste but wanted we wanted to be extra cautious and go beyond the - our state health department basic requirements. And they were happy with this.

Dr. Tim Uyeki:
Thanks Dr. Smith. Dr. Lyon and colleagues do you want to just comment about the - the question about the profuse diarrhea the issues about use of bedside commode or what to do with the soiled material and particularly the fecal matter and waste disposal?

Dr. Marshall Lyon III:
Yes Marshall Lyon from Emory University. We did a very similar protocol where they bedpan or the container from the bedside commode was dumped into the toilet with a predefined measure of a quaternary ammonium compound which inactivates the virus.

It was allowed to sit for a while before being flushed down. This satisfied our local sewer and our utilities company.

With subsequent patients we actually found a stool solidifier which we then could add that to the watery diarrhea and to the quaternary ammonium compound so that it, you know, was less for lack of a better term sloshy because we do worry in a shallow bedpan that there could be some splashing and inadvertent exposure even though all of our care providers were wearing full body protective equipment.

(Kathy Toumei):
Thank you.

Dr. Tim Uyeki:
Thanks Dr. Smith and Dr. Lyon. I’ll just mention that actually CDC waste management guidance is in progress and we hope that that will be posted in the near future.

Could we have the next question please?

Coordinator:
The next question is from (Brett Gordon). And please state your organization.

(Brett Gordon):
Oh hi. This is (Brett Gordon). I’m a physician in Chicago. And I was wondering if you could repeat the antiviral drugs which were used in Nebraska?

Dr. Tim Uyeki:
Dr. Florescu would you like to mention the kind of interventional therapies that were given to your patients?

Dr. Diana Florescu:
Yes for one patient we used Brincidofovir and for the other patient we used Tekmira - TKM-100802. And of course both patients received convalescent plasma.

Dr. Tim Uyeki:
Thank you very much. I would just mention that these are investigational therapeutics. These were not given as part of any controlled trial. They were given for either emergency IND approval from the FDA or through an IND through one of the companies through FDA approval.

Dr. Lyon do you want to just mention again the kinds of therapies that were given to your patients?

Dr. Marshall Lyon III:
Absolutely. So we used a convalescent sera from - or more correctly plasma from recovered patients. Then we used ZMapp which I described earlier which is a monoclonal antibody, three monoclonals combined into a single product.

We used the TKM Ebola product which is a small interfering RNA from Tekmira is the company. And then finally we have been using Brincidofovir which is a lipid formulation of the antiviral cidofovir. Over.

Dr. Tim Uyeki:
Thank you Dr. Florescu and Dr. Lyon. This is Tim Uyeki from CDC. I’ll just mention that although you’ve heard about several patients who received convalescent plasma treatment we do not know the effectiveness of this in terms of either clinical benefit or virologic benefit.

And again it’s impossible to know in uncontrolled use. But there are there’s a lot of interest in convalescent plasma treatment as you probably are aware of and there are studies that are proposed to be implemented in West Africa.

What’s really needed are controlled clinical trials of convalescent plasma treatment. But at this point we don’t have data from such trials and we really don’t know of the specific benefit of convalescent plasma treatment.

There are definitely issues about when is an optimal time to sample the recovered patient to optimize the level of neutralizing antibodies for example in plasma, in the donor plasma.

And so there’s a lot of work that is still needed to understand the kinetics of the neutralizing antibody response to this particular virus, when is the optimal time to sample and for the donor to donate plasma.

And then certainly in controlled trials what would be the benefit if any? And this is another area that we really need data for.

But I think it’s very, very difficult to draw inferences in the single patient use. And most of these patients receive more than one therapeutic.

Next question please.

Coordinator:
The next question is from (Darla Sullavet). And please state your organization.

(Darla Sullavet):
Yes Flowers Hospital in (Devon), Alabama. My question is to the affiliates from Emory the nurses that had the gear and they would swap out, how many hours did they actually stay in with the patient? And then my second question is to the sponsor of this call. It says it will be recorded a few days after so can we expect the recording by this Friday?

Dr. Tim Uyeki:
Dr. Lyon and colleagues would you like to address the first question?

Dr. Marshall Lyon III:
Absolutely. This is Marshall Lyon at Emory University. We allowed our nurses to stay in the full body protection for up to four hours.

So that includes the powered air purifying respirators. Without that I think we would limit our personnel in the room to probably one hour if we were using masks and face shields which are adequate. They’re just not as comfortable as the PAPRs that we used.

This is Loretta with the Clinician Outreach and Communication Activity, COCA. Please check the Web site in a few days and you will find the recorded audio to this call and the call transcript.

Dr. Phil Smith:
This is Phil Smith...

Dr. Tim Uyeki:
Yes.

Dr. Phil Smith:
...from Nebraska. We had somewhat similar experience and although our - we found that our nurses with face shields and N95 and the rest of the full gear were comfortable. We found the right mix of PPE that they were comfortable for up to three or four hours.

And we kind of let them decide during that period of time when they would come out.

They would often rotate out and become a doffer for four hours and then rotate back in again. Over.

Dr. Tim Uyeki:
Thanks Dr. Smith and Dr. Lyon. Can we have the next question please?

Coordinator:
The next question is from Dr. (Bufmeyer). And please state your organization.

(Bufmeyer):
Yes. This is Dr. (Bufmeyer) I’m in the Tampa Bay area with One Blood. And I’m the medical director for several transfusion services in the area.

And in the process of the laboratories determining how to handle samples most of our hospitals have elected to go with the Emory protocol.

But I’m curious about the use of what we would call emergency relief or universal - universally compatible red cells and AB plasma.

Did you maintain this policy throughout the hospital stay? How many blood components on average can we expect these patients will need? And what was your plan in the event of a transfusion reaction and handling the workup for those?

Dr. Tim Uyeki:
Dr. Florescu and Dr. Smith would you like to address that?

Dr. Phil Smith:
I don’t know that we can. I think I think that maybe should go to Emory. But we did transfuse plasma. We did not have to transfuse platelets here. And the plasma was appropriately matched by blood type and we did not - we had preparations were made for a transfusion reaction but we did not encounter one. Over.

Dr. Tim Uyeki:
Thanks Dr. Smith. Dr. Lyon could you take that question?

Dr. Marshall Lyon III:
Yes. This is Dr. Lyon in Emory. I think that we used our sort of massive transfusion protocols for trauma with O neg blood.

We had to give some red cells and platelets in terms of components. Honestly I don’t know what we would do if we had a transfusion reaction because all of our testing was done here in the unit.

We probably would have asked some support from our transfusion pathologist. But I’m not sure exactly what protocol they would follow to try to work that out. Over.

Dr. Tim Uyeki:
Thanks. Could we have the next question please?

Coordinator:
The next question is from Carlton Stadler. And please state your organization.

Carlton Stadler:
This is Carlton Stadler from Bon Secour Court Health System in Richmond, Virginia. My question involves emergency room care and I’m not sure if any of your colleagues can address preparation for the arrival of these patients. Were they taken straight to units? And even I guess through the screening process did you all have tents set up outside or did you find it more optimal to use space in the department?

Dr. Tim Uyeki:
Yes I’m not sure we’re going to address those kinds of questions on this call but we do have guidance and we have additional new guidance that will be posted soon and hopefully will address some of that. I wonder if we could just focus on clinical management? Maybe we could have the next question please?

Coordinator:
Thank you. The next question is from Robert Volk and please state your organization.

Robert Volk:
Hi. Robert Volk from Rush University in Chicago. In our preparations for such an event we realized with our Type II equipment we can’t use stethoscopes and other devices to help us examine the patient to auscultate, you know, ET tubes are in the right position or NG tubes are inserted so how did you accomplish all this?

Dr. Tim Uyeki:
Nebraska colleagues would you like to respond?

Dr. Phil Smith:
Yes we - this is Phil Smith. We experimented with several brands of volume accentuated, I’ll call them stethoscopes and eventually settled on one that’s a small disk. And when during a donning process one puts on earplugs that are between layers of coverage so they do not contact your skin.

We go into the room and there’s a jack that plugs into the small disk like scope with significant volume augmentation. Ones able to heart sounds, breath sounds and bowel sounds quite satisfactory.

When one completes the exam the nurse puts on a clean pair of gloves and removes them from the ear with fairly readily without much difficulty. And we found this to be a good system.

Robert Volk:
What was the name of that?

Dr. Phil Smith:
I believe it is the video V-I-D-Y-I-O or Y-E-O video system.

Robert Volk:
Thank you.

Dr. Tim Uyeki:
Dr. Lyon would you like to comment?

Dr. Marshall Lyon III:
That’s a much better system than we had. We did use a portable x-ray machine. With our digital imaging processing we were able to wrap the plates in a couple layers of plastic or, you know, inside a plastic bag and then shoot a film to guarantee the place or adequate placement of central lines in OG or NG tubes and then develop those. And we could look at those on our computer system so that it was relatively easy to do.

The machine itself, the x-ray machine never contacted the patient. Obviously we had an extension seat or arm that we could put in that could get close enough to the patient.

The other thing we could do is to using a regular stethoscope listening to through our PAPR hood if you briefly unplug the power supply to the PAPR that will make it more quiet. And then you can listen through the stethoscope.

Of course then you plug your PAPR back in that has to be done through the Tyvek. So it could be a little clumsy. And if you’re plug comes all the way out you could lose it.

So that may not necessarily be the easiest way to do it. Sounds like the augmented system at Nebraska would be the way to go.

Dr. Phil Smith:
Although Marshall, let me chime in, Phil Smith here, that we did that without PAPRs. We - in both of our patients we were able to go without PAPRs which we would have used in a patient like the one you described that had lots of stool and bloody vomits. So I do not know of a good system that would be compatible with the PAPR system.

Robert Volk:
Thank you.

Dr. Tim Uyeki:
Thanks Dr. Smith. Dr. Lyon do you want to just comment about disinfection of a stethoscope?

Dr. Phil Smith:
I’m sorry could your repeat that question for us?

Dr. Tim Uyeki:
Do you want to comment about disinfection of the stethoscope?

Dr. Phil Smith:
Thank you. Yes, we had quaternary ammonium wipes that were in the room. We also had alcohol and bleach containing wipes. And so we would wipe it down with one of these before and after use as well as frequent use of alcohol hand sanitizers on our gloved hands.

Dr. Tim Uyeki:
Thank you. Could we have the next question please?

Loretta Jackson-Brown:
And operator before we go to the next question can you let me know how many questions are in the queue?

Coordinator:
Certainly, one moment. Looks like we have about 14 in queue right now.

Loretta Jackson-Brown:
Okay Dr. Uyeki how would you like to proceed knowing we have 14 questions in the queue?

Dr. Tim Uyeki:
Let’s try to take about five more depending upon the time. I don’t think we’re going to quite be able to take all 14 as our colleagues have clinical responsibilities they need to get to. So let’s try to take three to five more.

Coordinator:
Okay, the next question is from (Stewart Wise) and please state your organization.

(Stewart Wise):
Yes this is Dr. (Stewart Wise), Med Rep Consulting in New York.

I was wondering if you could comment a little bit more about the viral shedding question specifically about saliva, tears, semen and then vomiting and diarrhea. How long do they shed virus and how we handle a patient’s post-hospitalization?

Dr. Tim Uyeki:
Dr. Smith or Dr. Florescu would you like to comment about sampling and testing of different clinical specimens?

Dr. Phil Smith:
I’ll defer to my Emory colleagues who I think did more extensive testing than we did.

Dr. Tim Uyeki:
Okay, great. Marshall and colleagues would you like to comment about the testing that was done for different types of clinical specimens and viral RNA detection?

Dr. Marshall Lyon III:
Absolutely. Thank you for the question.

We did test skin, sweat, not specifically tears. But we did look at respiratory secretions, vomitus and stool.

Those - so vomitus and stool were positive at the time of the gastroenteritis which also probably corresponds to the highest level of viremia that patients experience.

They of course quit producing these specimens before their blood is cleared. So it’s hard to know whether, you know, gastric contents would be still virus positive or not.

We had only a transient viremia that was detectable in the skin/sweat of a patient. And this was negative well before the blood was negative.

As stated early on urine seemed to lag behind somewhat of blood in terms of clearance but not by many days. And semen is really known from previous studies to be positive out to 70 days. Over.

Dr. Tim Uyeki:
Yes, Dr. Lyon could you just clarify what type of testing was done for your - when you’re commenting upon the different types of clinical specimens here what is the testing that is reflected?

Dr. Marshall Lyon III:
Absolutely, my apologies. That was positive by RT-PCR and measuring the RNA of Ebola virus. And it was by that system that I mentioned earlier, the BioFire system which is not FDA approved for this purpose.

Dr. Tim Uyeki:
So this is Tim Uyeki. We have tested some specimens by certainly plasma specimens as well as urine specimens for real-time RT-PCR. And we are following that particularly to be able to document the clearance of viremia which is as Dr. Lyon mentioned earlier we would want to see two consecutive blood specimens collected more than 24 hours apart to both be negative by real-time RT-PCR as one criterion for discharge in addition to clinical recovery.

In terms of the question about testing issues or infectious issues after discharge, once the patients have resolved their viremia there would not be a requirement for additional testing of blood or any other clinical specimens.

However, as Dr. Lyon noted from past studies, limited data in the literature - there can be prolonged detection of Ebola virus RNA in semen. The seminal fluid is a immunologically protected site, the testes. And so this is what is observed. And but detection of viral RNA does not necessarily mean the detection of viable virus.

There is one report in the literature where virus has been isolated from semen at up to day 82 of illness. However that’s, you know, very limited data.

And so the recommendation for adolescent and male patients at the time of discharge is to abstain from sex or to use condoms for three months after the time of discharge. This is to be somewhat conservative because of the potential for the persistence of viable virus in the semen. Could we have the next question please?

Coordinator:
Thank you. The next question is from (Charla Itel). And please state your organization.

(Charla Itel):
Oak Hill Hospital in Brooksville, Florida.

Dr. Tim Uyeki:
I’m sorry, we can’t hear you. Could you repeat the question please?

(Charla Itel):
Yes sir. I was wondering if you could tell me if you know what hospital or how many hospitals will be available for transport of patients? Say we have a patient we’re screening or and they are - become positive. Is it to be presumed that we will be transferring them to higher level care hospitals?

Dr. Tim Uyeki:
Yes thank you for that question. We’re actually trying to address clinical management on this call. And I would direct that question to your state health department. Thank you.

(Charla Itel):
Okay, thank you very much.

Dr. Tim Uyeki:
Could we have the next question please?

Coordinator:
The next question is from (Marie Moss) and please state your organization.

(Marie Moss):
Hi. This is (Marie Moss) from (Mount Sinai Beth) Israel. And my question is just to go back when the central line, what kind of a central line was placed and under who placed it and what were the conditions and that was - was that the one that actually came out in transport? How did it work out with the central line? At what point in the hospitalization was it placed?

Dr. Tim Uyeki:
I’m going to ask Dr. Lyon and Dr. Connor to comment regarding the Emory patients.

Dr. Marshall Lyon III:
This is Marshall Lyon at Emory. So it was not a central line which came out during transport. It was actually a peripheral IV which came out during transport. And because of the subcutaneous (edema) the transport team was unable to secure another peripheral IV.

In terms of the brands of central lines I’m not entirely sure what brand we use. These were double lumen catheters which were placed into the internal jugular vein of the patients. As mentioned earlier this was done with ultrasound guidance. It was done under sterile conditions so that with full body drapes. And that’s it. Over.

Dr. Tim Uyeki:
Let me just see if Dr. Connor wanted to add anything to that?

Dr. Michael Connor:
Sure yes. So as far as central lines go I think that we have to recognize that this form of invasive procedure does have some potential risk of spillage of infectious blood and material. So care should be taken in setting up the room and covering surfaces that are exposed that might go a bit beyond the standard recommended full body drape and full barrier precautions that we typically use in the intensive care unit.

We use Arrow catheters, Arrow brand catheters but I don’t think the brand is really that important.

The IJ site is probably preferable just largely because that is sort of well recognized to be the most compressible site in patients with bleeding diatheses.

If one if being placed and a patient is becoming critically ill I would probably anticipate that you have a high likelihood of needing dialysis at least based on the experience so far.

And so if one is not being placed until the patient is progressing we probably would say place the central line on the left IJ and preserve the right IJ which is clearly preferred for dialysis access down the line.

I did want to make one comment on this one other question that somebody asked as far as the structure of the team.

You know, I think one of the things that’s really important as one designs their team is to recognize that the goal should be to limit the number of clinicians that need to - that truly need to enter the room on a daily basis.

So many consultants can do a lot of the work without direct physical exams especially if another provider has done a thorough physical exam and can relay that for the day.

The other thing to be - is that the intensivists, you know, we - we’ve had our anesthesia colleagues involved just in our initial sort of planning as we thought through this. But it should be recognized that almost all the procedures that will need to be done on these patients can be done by most critical care intensivists including intubations and bronchoscopies, chest tube insertions and that sort of stuff should any of that be required including central line access.

So in an effort to sort of decrease exposures to the rooms, I’m not sure that one needs to have sort of a separate trained corps of sort of anesthesia (or proceduralists) folks to help with airway management if your intensivists can do that as well.

Dr. Tim Uyeki:
Thanks Dr. Connor. I think we have time for one last question.

Coordinator:
Thank you. The next question is from Dr. (Michelle Halprin).

(Michelle Halprin):
Montefiore New Rochelle in New York. I had a question about the appearance of the cough. Does it occur very early on in the syndrome or after the gastroenteritis phase and would that somehow skew our management as far as use of antibiotics for example?

Dr. Tim Uyeki:
Nebraska colleagues would you like to comment on the cough and when in the clinical course and management, over?

Dr. Diana Florescu:
This is Nebraska. The cough occurred about nine days into the clinical illness. And we saw chest x-ray changes, pulmonary infiltrates, bilateral pulmonary infiltrates. And these we saw in both patients, consistent more with pulmonary edema.

And this was more consistent probably with capillary leak. We closely monitored the patient. On physical exam we found some crackles at the baseline.

We clinically monitored the patient. We did not start antibiotics. Patients were not hypoxic. And we did not start antibiotics and patient got better after four, five days.

We managed the cough with Dextromethorphan PRM. And there were no additional interventions for the cough.

(Michelle Halprin):
Thank you. May I ask another question?

Dr. Diana Florescu:
Yes.

(Michelle Halprin):
Were there any risk factors to the complications you mentioned such as the neuropathy or the acute renal insufficiency?

And would you like as a follow-up of that question would you for example restrict any healthcare workers based on their past medical history for caring for these patients?

Dr. Diana Florescu:
Our patients did not have acute renal failure.

Dr. Phil Smith:
I will say - this is Dr. Smith. The infection control concern we had was in patients who had vomiting and then had cough. And in both cases it was a dry cough. We - this raised some concern about droplets. And so it was just something we were prepared for but I think has to be taken into consideration.

Dr. Tim Uyeki:
Thanks Dr. Florescu and Dr. Smith. Dr. Lyon or colleagues would you like to just comment about the question about cough?

Dr. Marshall Lyon III:
Our patients didn’t have cough but I will comment on the question about risk factors for some of these other complications. None of our patients had any risk factors. They were all previously healthy.

And as far as staff, I think, you know, one of the big things is in addition to the skill set that they bring to the table and the care of the patient that getting in and out of PPE the more complicated it is the more dexterity that’s required on the part of the practitioner.

And one of the things that should be primary or paramount among anybody who is involved in this should be that they can not only put on the PPE correctly but they can take off the PPE correctly without contaminating themselves.

And I would say that the other thing that I would like to let the listeners know is that we have actually just posted today all of our protocols and standard operating procedures to our external Web site which is available at www.emoryhealthcare all one word. And that is Emory with an O .org forward slash ebolaprep.

You can access that through our main Web page at Emoryhealthcare.org. And that again does have all of our protocols and SOPs. And soon we’ll have videos with regards to putting on and taking off personal protective equipment.

Dr. Tim Uyeki:
Dr. Lyon thanks very much and...

Dr. Michael Connor:
This is - sorry Dr. Uyeki. This is Mike Connor. Just to answer the question about coughs, so our patient developed respiratory failure and respiratory distress with the similar interstitial infiltrate about the same time that is being referred to by the Nebraska cases around day nine, day eight, day nine, day ten. In that range is when we developed that.

He did not develop cough but did have marked respiratory distress and tachypnea with increased difficulty of breathing prompting the intubation.

Dr. Tim Uyeki:
Thank you very much Dr. Connor. And so with that I think we’ll end the question and answer period.

And just to make a few comments I think you’ve heard a lot about the clinical course, the complications, the different kinds of clinical management issues that are needed to be addressed with these Ebola virus disease patients.

Clearly this just reflects a very small number of patients that have been managed. But the real challenge is to improve clinical management of patients in West Africa in a resource - lower resource settings.

And we hope that the - some of the lessons learned in the sort of more aggressive and detailed clinical management and supportive care patients with Ebola virus disease in the US as well as from our colleagues in European centers can actually help improve and inform the clinical management of patients in limited lower resource settings in West Africa.

And so we do need much more clinical data both in the West African setting but also in those who have been managed outside of West Africa.

And with that I’d really like to thank our presenters and commenters on this call in particular Dr. Diana Florescu and Dr. Phil Smith of the University of Nebraska Medical Center and then Dr. Marshall Lyon, Dr. Michael Connor and Dr. Harold Franch of Emory University Hospital for their time and their presentations and also thank them very much for their care of their Ebola virus disease patients.

And so with that I’d like to turn it over back to Loretta and just thank all the participants and those listening in. Thank you very much.

Loretta Jackson-Brown:
On behalf of COCA we would like to thank everyone for joining us today with a special thank you to our CDC, Emory Healthcare and Nebraska Medical Center colleagues.

The recording of this call and the transcript will be posted to the COCA Website at Emergency.cdc.gov/coca within a few days.

A link to the Emory Healthcare Ebola Resources will be available from this call page. Look under Additional Resources.

To receive information on upcoming COCA calls subscribe to COCA by sending an email to coca@cdc.gov and write subscribe in the subject line.

Thank you again for participating in today’s COCA call. Have a great day.

Coordinator:
Thank you. This does conclude today’s conference. Thank you for joining. You may disconnect at this time.

END