Supplementary appendix

Supplementary appendix
This appendix formed part of the original submission and has been peer reviewed.
We post it as supplied by the authors.
Supplement to: Wolf T, Kann G, Becker S, et al. Severe Ebola virus disease with vascular
leakage and multiorgan failure: treatment of a patient in intensive care. Lancet 2014;
published online Dec 19.
Fluid Resuscitation Electrolyte Supplementation Oxygen Therapy Non‐invasive Ventilation Invasive Ventilation Renal Replacement Therapy Antimicrobial Therapy Liberia 2 – 5 litres per day plus oral intake 80 – 100 mmol oral or intravenous potassium per day 2 litres per minute ‐ ‐ ‐ ? Liberia 2 ‐3 litres per day plus oral intake 60 – 80 mmol potassium chloride per day 1 – 3 litres per minute ‐ ‐ ‐ Ceftriaxon, Azithromycin, Levofloxacin Parra MJ et al. [2] Spain 500 ml isotonic saline in first hour, 500 ml over next 4 hours 500 ml isotonic saline plus Potassium Chloride ever hour ‐ ‐ ‐ ‐ ? Kreuels B et al. [3] Sierra Leone 8000 ml per day over first 3 days 8 – 10 mmol potassium chloride per hour ‐ ‐ Ceftriaxon Meropenem, Vancomycin, Conner MJ et al. [4] Sierra Leone Received aggressive fluid resuscitation, precise volumes not given 11 days 14 day CRRT, 13 days intermittent RRT ? 14 days 19 days CRRT 10 days intermittent RRT Imipenem/Cilastin, Meropenem, Colistin, Metronidazole, Tigecyclin, Anidulafungin, Fluconazole Country of Infection Lyon GM et al. [1] Wolf T et al. Sierra Leone Positive fluid balance of 4,100 ml on first day (day 6) ? 5 – 10 mmol potassium chloride per hour + 8 days + ‐ 2‐3 litres per minute 6 hours before, 12 hours after invasive ventilation Supplementary Table1: Putting Research into context. Intensive Care strategies applied in 6 cases of EVD patients treated in the U.S. and Europe. CRRT = continous renal replacment therapy, RRT = renal replacement therapy. PANEL PUTTING REASEARCH INTO CONTEXT SYSTEMATIC REVIEW We conducted a search on recent publications on the clinical management of EBOV patients who were critically ill and were treated outside the epidemic region with intensive care therapy. PubMed and ProMed‐mail web engines were used to identify the four cases. Two patients from Liberia had been treated in the US [1] and one patient who acquired EVD outside Western Africa in Spain [2]. In all cases, aggressive volume and electrolyte substitution due to severe intravascular volume depletion and one in Spain. Although not many features of intensive care therapy were required, a central line and careful electrolyte monitoring were applied in the US patients [1]. Another patient from Sierra Leone, who was treated in Hamburg, was more profoundly ill with severe diarrhoea and 10 litres of volume substitution in the first 72 hours, and a development of gram‐negative Septicaemia and respiratory failure later in the disease, requiring non‐invasive ventilation for 8 days. Another patient from the U. S. required invasive ventilation and renal replacement therapy [4]. INTERPRETATION The intensive volume supplementation described has a risk of translocation of fluids into the third space in case of VLS. Whereas this was not described in the US and the Spanish patient, it was seen as a contributing factor for the respiratory failure in the Hamburg patient. VLS was documented in our case and led to invasive ventilation. This demonstrates, that the adjustment of volume therapy to respiratory function then becomes necessary. Tachypnoea and renal failure have been described as a negative prognostic factor in EVD patients from Sierra Leone [5]. In addition to invasive ventilation, our patient required RRT. FX06 was applied in the attempt to optimize supportive therapy for the first time in EVD to our knowledge. It was possible to manage the patient successfully with these combined measures of intensive care therapy. 1. Marshall GL, Mehta AK, Varkey JB, et al. Clinical Care of Two Patients with Ebola Virus Disease in the United States. NEJM November 12, 2014, DOI: 10.1056/NEJMoa1409838 2. Parra MJ, Salmeron OJ, Velasco M. The First Case of Ebola Virus Disease Acquired outside Africa. NEJM November 19, 2014, DOI: 10.1056/NEJMc1412662 3. Kreuels B, Wichmann D, Emmerich P, et al. A Case of Severe Ebola Virus Infection Complicated by Gram‐negative Septicaemia. NEJM October 22, 2014, DOI: 10.1056/NEJMoa1411677 4. Conner MJ, Kraft C, Mehta AK et al. Successful Delivery of RRT in Ebola Virus Disease. JASN November 14, 2014, DOI: 10.1681/ASN.2014111057 5. Schieffelin J, Shaffer JG, Goba A et al. Clinical Illness and Outcomes in Patients with Ebola in Sierra Leone. NEJM October 29, 2014, DOI: 10.1056