Safety and efficacy of combined Extracorporeal CO2 Removal and Renal Replacement therapy in patients with Acute Respiratory Distress Syndrome and Acute kidney Injury.
the pulmonary and renal support in ards (parsa) study
Jérôme Allardet-Servent, MD, MSc1; Matthias Castanier, MD1; Thomas Signouret, MD1, Rettinavelou Soundaravelou, MD1, Anne Lepidi, MD1, Jean-Marie Seghboyan, MD1
SUPPLEMENTAL DIGITAL CONTENT
Materials and Methods
1. Inclusion criteria:
- Presence of an Acute Respiratory Distress Syndrome as defined by the Berlin criteria 1:
o Acute onset of symptoms (< 1week) of a known clinical insult and
o Bilateral opacities on Chest-X ray and
o Pulmonary edema not fully explained by cardiac failure or fluid overload and
o PaO2/FIO2 < 300 with PEEP ≥ 5 cmH2O for mild, < 200 for moderate and < 100 for severe ARDS.
- And Presence of stage 2 or stage 3 Acute Kidney injured as defined by KDIGO 2:
o Increase in serum creatinine > 2 times baseline within the prior 7 days (> 3 times baseline or ≥ 40 g/l for stage 3) or
o Urine output ≤ 0.5 ml/kg/h for ≥ 12 h (≤ 0.3 ml/kg/h for ≥ 24 h or anuria for ≥ 12 h for stage 3)
2. Exclusion criteria:
- Severe hypoxemia as defined by PaO2/FIO2 < 60 with PEEP ≥ 18 cmH2O
- Death expected within 72 hours
- Heparin allergy
- Intracerebral hemorrhage or intracranial hypertension
- Unaccess to superior vena cava sites due to thrombosis or infection or others
- Lack of written informed consent from next of kin
3. Formulae and calculations
3.1. Parameters derived from blood gases
Blood gases were analyzed immediately after drawing using a RapiLab 1265 blood gas analyzer (Siemens Healthcare Diagnostics, Deerfield, IL).
· Actual bicarbonate was calculated according to the manufacturer (Siemens) as:
HCO3–act (mmol.l-1) = 0.0307 × PCO2 × 10(pH(37) – 6,105)
With PCO2 for carbon dioxide tension
· Total oxygen blood content was defined as:
CtO2 (ml.dl-1) = (Hb × 1.39 x SO2) + (0.0031 × PO2)
With Hb for hemoglobin (g.dl-1), SO2 for oxygen saturation of hemoglobin (%) and PO2 for oxygen tension (Torr).
· Total carbon dioxide blood content was defined as:
CtCO2 (mmol.l-1) = (0.0307 × PCO2) + HCO3–act
With PCO2 for carbon dioxide tension (Torr).
· CO2 removal by the membrane oxygenator was calculated as 3-5:
CO2 removal rate (ml.min-1) = 22.4 × Qflow × (CtCO2 inlet – CtCO2 outlet)
With Qflow for inlet oxygenator blood flow (l.min-1) and CtCO2 for total carbon dioxide blood content at inlet and outlet of oxygenator (mmol.l-1).
· O2 uptake by the membrane oxygenator was calculated as 3-5:
VO2 (ml.min-1) = Qflow × (CtO2 inlet – CtO2 outlet)
With Qflow for inlet oxygenator blood flow (L.min-1) and CtO2 for total oxygen blood content at inlet and outlet of oxygenator (ml.dl-1).
3.2. Respiratory parameters
· Static respiratory system compliance was defined as :
CRS (ml.cmH2O-1) = TV / (Pplat – PEEPtot)
With TV for tidal volume (ml), Pplat for plateau pressure (cmH2O) and PEEPtot for total positive end-expiratory pressure (cmH2O).
· Dead space fraction of tidal ventilation (VD/VT) was calculated according to the Enghoff modification of the Bohr equation:
VD/VT (%) = (PaCO2 – PEtCO2) / PaCO2
With PaCO2 for arterial carbon dioxide tension and PETCO2 for end-tidal CO2 tension (Torr).
3.3. RRT-derived parameters
RRT-derived parameters were recorded from the PrismaFlex monitor.
· Filtration fraction (FF) was calculated according to the manufacturer (Gambro) as:
FF (%) = 100 × (QPost + QFR) / (Qplasma + QPre)
With Qplasma = [1 – (Htc / 100)] × Qblood
With Qpost for post-dilution flow rate, QFR for fluid removal flow rate, Qplasma for plasma flow rate, Qpre for pre-dilution flow rate, Qblood for blood flow rate and Htc for hematocrit.
· Trans-membrane pressure was calculated according to the manufacturer (Gambro) as:
PTM (mmHg) = [(Pfilter inlet + Pfilter outlet) / 2] – Peffluent
With Pfilter for the inlet and outlet pressure of hemofilter and Peffluent for the pressure in the effluent compartment.
4. Study Protocol
4.1. Management of PEEP and FIO2
PEEP and FIO2 were modified according to the PEEP/FIO2 table of the ARDS Net protocol (ARMA trial) if 6:
- SpO2 remains < 88 % or PaO2 < 55 Torr after a recruitment maneuver (i.e., 2 cmH2O stepwise increase in PEEP until Pplat = 35 cmH2O).
- Or SpO2 remains > 95 % or PaO2 > 80 Torr for > 10 min.
The PEEP/FIO2 table of the ARDS Net protocol is represented below:
FIO2 / 0.3 / 0.4 / 0.4 / 0.5 / 0.5 / 0.6 / 0.7 / 0.7 / 0.7 / 0.8 / 0.9 / 0.9 / 0.9 / 1PEEP / 5 / 5 / 8 / 8 / 10 / 10 / 10 / 12 / 14 / 14 / 14 / 16 / 18 / ≥ 18
4.2. Management of the pump blood flow and the effluent flow
The pump blood flow and the effluent flow were modified according to the following pressure measured within the hemofiltration circuit:
- Inlet arterial pressure (Part) corresponds to the negative pressure measured upstream of the blood pump and warns on the permeability of the arterial lumen of the catheter. Part is decreased when the pump blood flow is decreased.
- Pressure drop (Pdrop) corresponds to the difference in the pressure measured at the inlet and the outlet of the hemofilter. It is influenced by the pump blood flow and by the pressure downstream of the hemofilter. It warns on the presence of thrombosis (clotting) within the hemofilter or any increase in distal pressure (venous side of the catheter mainly or tube’s kinking). Pdrop is decreased when the pump blood flow is decreased.
- Trans-membrane pressure (TMP) corresponds to the difference in the mean pressure between the blood side and the effluent side of the hemofilter. It is influenced by the pump blood flow and by the effluent flow. It warns on the degree of permeability of the hemofilter (clogging). TMP is decreased when the pump blood flow is increased or when the effluent flow is decreased.
In our protocol, the pump blood flow was progressively increased until its maximum value: 450 ml.min-1 minus the pre-dilution rate. The effluent flow was settled at 45 ml.kg-1.h-1 with a pre-dilution rate of 33 %. Our management of pump blood flow and effluent flow was the following:
- If Part was > -220 mmHg: stepwise 20 ml.min-1 reduction of the pump blood flow until Part < -220 mmHg. If a pump blood flow below 350 ml.min-1 was required to maintain Part < -200 mmHg, the catheter was rinsed and then replaced or exchanged with a longer one (24-cm).
- If Pdrop was > 200 mmHg: stepwise 20 ml.min-1 reduction of the pump blood flow until Pdrop < 200 mmHg and verification of the permeability of the venous side of the catheter or the absence of tube’s kinking.
- If TMP 300 mmHg è depends on the associated Pdrop:
o If TMP > 300 and Pdrop > 200: stepwise 20 ml.min-1 reduction of the pump blood flow until Pdrop < 200 mmHg AND stepwise 150 ml.h-1 reduction of the effluent flow (with 100 ml.h-1 post-dilution and 50 ml.h-1 pre-dilution) until TMP < 300 mmHg.
o If TMP > 300 and Pdrop < 200: stepwise 20 ml.min-1 increment of the pump blood flow until TMP < 300 mmHg or until maximum pump blood flow value. If done, stepwise 150 ml.h-1 reduction of the effluent flow (with 100 ml.h-1 post-dilution and 50 ml.h-1 pre-dilution) until TMP < 300 mmHg.
References
1. Ranieri VM, Rubenfeld GD, Thompson BT, et al. Acute respiratory distress syndrome: the Berlin Definition. JAMA. 2012;307(23):2526-2533.
2. KDIGO Work Group. KDIGO clinical practice guideline for acute kidney injury. Kidney Int Suppl. 2012;2:1-138.
3. Kawahito S, Maeda T, Motomura T, et al. Development of a new hollow fiber silicone membrane oxygenator: in vitro study. Artif Organs. 2001;25(6):494-498.
4. Kawahito S, Maeda T, Takano T, et al. Gas transfer performance of a hollow fiber silicone membrane oxygenator: ex vivo study. Artif Organs. 2001;25(6):498-502.
5. Kawahito S, Haraguchi S, Maeda T, et al. Preclinical evaluation of a new hollow fiber silicone membrane oxygenator for pediatric cardiopulmonary bypass: ex-vivo study. Ann Thorac Cardiovasc Surg. 2002;8(1):7-11.
6. Ventilation with lower tidal volumes as compared with traditional tidal volumes for acute lung injury and the acute respiratory distress syndrome. The Acute Respiratory Distress Syndrome Network. N Engl J Med. 2000;342(18):1301-1308.
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