Abstract
Background
Low-flow extracorporeal CO 2 removal (ECCO 2 R), managed using a renal replacement platform, is useful in achieving lung-protective ventilation with low tidal volume. However, its capacity for CO 2 elimination is limited. Whether this system is valuable in reducing strong inspiratory efforts in respiratory failure is unclear. The combined use of alkaline agents with low-flow ECCO 2 R might be useful in hypercapnic subjects preserving inspiratory efforts.
Methods
This study examined the effects of low-flow ECCO 2 R on respiratory status and investigated the effects of NaHCO 3 , trometamol, and saline on respiratory status during low-flow ECCO 2 R in CO 2 inhalation models.
Results
Although low-flow ECCO 2 R did not significantly change the respiratory rate (92.2% ± 24.3% [mean ± standard deviation] of that before ECCO 2 R), it reduced minute ventilation (MV) (78.9% ± 13.5% of that before ECCO 2 R). The addition of NaHCO 3 improved acidemia but did not change MV compared with that of the saline group (0.451 ± 0.026 L/min/kg body weight [BW] vs. 0.556 ± 0.138 L/min/kg BW, respectively). The addition of trometamol improved acidemia and reduced MV compared with that of the saline group (0.381 ± 0.050 L/min/kg BW vs. 0.556 ± 0.138 L/min/kg BW, respectively). The total amounts of CO 2 removed during ECCO 2 R in the NaHCO 3 group were lower than those in the saline and trometamol groups.
Conclusion
The low-flow ECCO 2 R reduced MV in subjects preserving spontaneous breathing efforts with CO 2 overload. The addition of NaHCO 3 improved acidemia but did not change MV, whereas the addition of trometamol improved acidemia and reduced MV.
Keywords: extracorporeal CO2 removal , hypercapnia , inspiratory effort , NaHCO3 , trometamol
Introduction
In patients with lung injury, the large tidal volume (VT) and increased transpulmonary pressure caused by strong spontaneous breathing efforts can exacerbate the lung injury. 1 - 3 Extracorporeal membrane oxygenation (ECMO) reduces strong inspiratory efforts by eliminating carbon dioxide (CO 2 ). 4 - 6 Although the capacity of CO 2 elimination by ordinary ECMO is high, it required larger blood accesses, which are more invasive and restrict the patient’s activity. Extracorporeal CO 2 removal (ECCO 2 R) is less invasive and is easy to perform. ECCO 2 R is useful for achieving low VT ventilation. 7 , 8 Recently, low-flow ECCO 2 R is managed using a renal replacement platform, the blood of which was approximately 10 mL/kg body weight (BW)/min. 9 , 10 However, whether this system is valuable in reducing strong inspiratory efforts in respiratory failure is unclear. In addition, its capacity for CO 2 elimination is limited. The effects of the low-flow ECCO 2 R are reduced, especially in a patient with complicated metabolic acidosis.
Whether the increased spontaneous respiratory effort due to acidosis causes lung injury is unclear, but acidosis management is probably essential for respiratory care. 11 Reducing the partial pressure of CO 2 (PaCO 2 ) is a primary treatment goal for respiratory acidosis, but it can lead to lung injury by requiring high airway pressure and a marked increase in VT. In such cases, CO 2 removal by ECCO 2 R may be useful.
In addition, the administration of alkaline agents is an acute treatment option for acidosis. The combined use of alkaline agents and low-flow ECCO 2 R might be useful in hypercapnic subjects preserving inspiratory efforts. Sodium bicarbonate (NaHCO 3 ) is widely used as an alkaline agent. However, NaHCO 3 infusion produced specific amounts of CO 2 and reduced the effects of low-flow ECCO 2 R on hypercapnic acidosis. Trometamol is another alkaline agent that does not generate CO 2 . 12 - 14 In a study, trometamol was useful for correcting acidosis while avoiding CO 2 accumulation, and this contributed to a reduction in inspiratory effort and serum lactate. 15 Trometamol is considered more useful than NaHCO 3 as an alkaline agent during low-flow ECCO 2 R. This study examined the effects of low-flow ECCO 2 R managed using a renal replacement platform on respiratory status in CO 2 inhalation respiratory failure models with preserved inspiratory efforts. In addition, this study investigated the effects of alkaline agents in reducing strong inspiratory efforts during low-flow ECCO 2 R in CO 2 inhalation. The CO 2 inhalation models represented respiratory failure with enlarged dead spaces. The models were treated with NaHCO 3 , trometamol, and saline. Thus, the effects of NaHCO 3 and trometamol on respiratory status during low-flow ECCO 2 R were investigated in CO 2 inhalation models.
Methods
This study was approved by the Animal Experimentation Committee of Osaka University Medical School (approval no. 26-056-003). Animals were cared for according to the university standards for the care and use of laboratory animals.
Animal Preparation
Fifteen adult male New Zealand White rabbits (weighing: 2.96 ± 0.12 kg) were anesthetized with a continuous infusion of propofol (30–70 mg/kg/h) and tracheostomized with a tracheostomy tube (4-mm internal diameter). A 24-gauge catheter was placed in the right carotid artery to measure arterial blood pressure. A 7-Fr double-lumen catheter with a length of 10 cm (Duo-Flow; Medical Components, Inc., Harleysville, PA) was inserted via the right external carotid vein and used for low-flow ECCO 2 R. We controlled the sedation levels during the study by adjusting propofol dosages while monitoring the animals’ status as in previous reports. 2 , 3 , 16 The target sedation level was to maintain spontaneous breathing efforts without voluntary movement during the experiment. Intravenous fluid was provided via continuous infusion of lactated Ringer’s solution at 10 mL/kg/h. The respiratory flow was measured using a pneumotachometer (Model 4700; Hans-Rudolph, Kansas City, MO, USA) placed at the proximal end of the endotracheal tube. Pressures at the proximal end of the endotracheal tube (airway pressure [Paw]) were measured using a differential pressure transducer (TP603T; Nihon Kohden, Tokyo, Japan). All pressure transducers and pneumotachometers were calibrated at 10 cmH 2 O and 200 mL/s using a ventilator (NPB840; Medtronic, Minneapolis, MN, USA) under a fraction of inspired oxygen (FiO2) of 1.0. Inspiratory CO 2 content was measured at the inspiratory limb of the ventilatory circuit. Arterial blood gas measurements were recorded using a blood gas analyzer (ABL725; Radiometer, Copenhagen, Denmark).
Analyses using the WINDAQ software (Dataq Instruments, Akron, Ohio) produced the respiratory flow, Paw, and arterial pressure. Digital integration of the flow data yielded the ventilatory volume. Arterial pressure, base excess, electrolytes, and lactate data were measured to quantify hemodynamics. The minute ventilation (MV), respiratory rate (RR), PaCO 2 , pH, and partial pressure of oxygen (PaO 2 ) were recorded as measures of respiratory function. The anion gap was calculated using the following equations: Anion gap (mEq/L) = Na+ − Cl− − HCO 3 −.
CO2 Inhalation Model
The animals were ventilated using an NPB 840 (Medtronic, Minneapolis, MN, USA) set on the assisted pressure-controlled ventilation (PCV) mode at a PCV of 6 cmH 2 O, 2 cmH 2 O of positive end-expiratory pressure (PEEP), 0.5 s of inspiratory time, 10/min ventilation frequency, and a FiO 2 of 0.4. Inspiratory time was adjusted according to the RR. We used the CO 2 inhalation model of respiratory failure similar to a previous report. 16 The concentration of inhaled CO 2 was set at 4% throughout the study. The study flowchart to indicate the experimental procedures is shown in Fig. 1 . The low-flow ECCO 2 R was attached to the animals after 30 min of CO 2 inhalation. The settings of the low-flow ECCO 2 R were as follows: extracorporeal circulation was performed using a renal replacement platform (JUN-505; Japan Lifeline Co., Ltd., Tokyo, Japan) using an extracorporeal circuit for a child (JCH-22S; Japan Lifeline Co., Ltd., Tokyo, Japan). The circuit was connected to the membrane oxygenator (OxiaIC-N MO-IC-NEO-LC; JMS, Tokyo, Japan). Its membrane surface area was 0.21 m 2 . The total blood volume of the ECCO 2 R system was 54 mL. The ECCO 2 R system was primed with saline. The blood flow of the ECCO 2 R system was set at 10 mL/kg BW/min. The O 2 flow was adjusted to maintain the pH of the outflow blood to be less than 7.600.
Fig. 1 . Study flowchart.
ECCO 2 R: extracorporeal CO 2 removal.
Thirty minutes after initiating low-flow ECCO 2 R, the animals were randomly assigned to one of three alkaline agent groups (n = 5 per group): saline (control group), NaHCO 3 , and trometamol groups. The concentration of the alkaline solutions was set at 1 mEq/mL. Before the administration of the alkaline agents, arterial blood gas, and electrolytes were measured. The doses of the alkaline agents were as follows: 0.35 × (10 − base excess) × BW (mEq) for the first 15 min, followed by 0.35 × (10 − base excess) × BW (mEq/h) for the next 165 min. The total fluid infusion rate was set at 10 mL/kg/h by adjusting the amount of coinjected saline. MV, RR, pH, PaCO 2 , PaO 2 , HCO 3 −, base excess, anion gap, blood electrolytes, hemoglobin (Hb), lactate, and arterial pressures were recorded. All measurements were performed before the inhalation of CO 2 and after 30-min CO 2 inhalation, 30-min ECCO 2 R, and 180-min treatment with alkaline agents. The amounts of CO 2 removed were calculated using the CO 2 content of the inflow and outflow blood of the ECCO 2 R circuit. In addition, the volume of CO 2 in the administered NaHCO 3 was added to the calculation in the NaHCO 3 group.
Statistical Analyses
The mean values from 10 consecutive breaths after attaining a steady state were presented for each respiratory parameter. To compare the effects of the low-flow ECCO 2 R on CO 2 inhalation, repeated measures analysis of variance was performed between basal status, CO 2 inhalation, and low-flow ECCO 2 R. If statistically significant differences existed, multiple post-hoc comparisons were performed using Tukey’s honestly significant difference test. To examine effects of the alkaline agents during low-flow ECCO 2 R on CO 2 inhalation models, one-way analysis of variance was used between saline (control group), NaHCO 3 , and trometamol groups. If statistically significant differences existed, multiple post-hoc comparisons were performed using Tukey’s honestly significant difference test. For all analyses, p -values of less than 0.05 were considered statistically significant. All data were analyzed using JMP, version 14.0 (SAS Institute, Cary, NC, USA).
Results
Effects of the Low-Flow ECCO2R on CO2 Inhalation Models
Although low-flow ECCO 2 R did not significantly change the RR (92.2% ± 24.3% of that before ECCO 2 R), it reduced MV (78.9% ± 13.5% of that before ECCO 2 R). Compared with data before the attachment of ECCO 2 R, although ECCO 2 R increased PaO 2 and did not alter the PaCO 2 level, metabolic acidosis by hemodilution decreased the pH during ECCO 2 R. The attachment of ECCO 2 R decreased Hb due to the hemodilution by the saline in the ECCO 2 R circuit. In addition, the hemodilution reduced the mean arterial pressure by decreasing vascular resistance ( Table 1 ).
Table 1 . Characteristics at the basal status, CO 2 inhalation, and under extracorporeal CO 2 removal (ECCO 2 R) .
a Values are presented as mean ± standard deviation, with range in brackets.
bAnion gap = Na+ − Cl− − HCO3−
*significantly different in comparison with Saline, p < 0.05;
†significantly different in comparison with NaHCO3, p < 0.05.
BW: body weight.
|
Characteristic |
Base (n = 15) |
CO 2 inhalation (n = 15) |
ECCO 2 R (n = 15) |
p value |
|
Minute ventilation/BW (L/min/kg) |
0.383 ± 0.060 (0.293−0.462) |
0.718 ± 0.122 * (0.598−1.073) |
0.560 ± 0.098 * (0.398−0.769) |
< 0.0001 |
|
Respiratory rate (per min) |
38 ± 8 (27−52) |
55 ± 11 * (41−79) |
50 ± 12 * (35−77) |
< 0.0001 |
|
pH |
7.439 ± 0.037 (7.376−7.506) |
7.408 ± 0.042 * (7.325−7.481) |
7.347 ± 0.047 * † (7.244−7.441) |
< 0.0001 |
|
PaCO 2 (mmHg) |
34.0 ± 4.1 (24.0−41.2) |
37.8 ± 5.3 * (31.3−53.2) |
40.1 ± 4.6 * (33.1−50.5) |
< 0.0001 |
|
PaO 2 (mmHg) |
180 ± 7 (164−189) |
188 ± 10 * (171−201) |
204 ± 14 * † (176−225) |
< 0.0001 |
|
HCO 3 − (mEq/L) |
22.5 ± 2.1 (17.0−25.6) |
23.3 ± 2.8 (19.8−29.3) |
21.3 ± 2.5 † (16.7−25.8) |
0.0059 |
|
Base excess (mEq/L) |
−0.7 ± 2.1 (-5.3−2.9) |
−0.6 ± 2.7 (-5.3−3.9) |
−3.4 ± 2.7 * † (-8.3−2.1) |
< 0.0001 |
|
Anion gap (mEq/L) b |
4.7 ± 1.9 (1.0−7.9) |
3.3 ± 2.8 (-6.0−3.9) |
4.6 ± 2.7 (1.2−10.3) |
0.2040 |
|
Na+ (mEq/L) |
138 ± 4 (129−142) |
138 ± 4 (127−144) |
138 ± 3 (131−143) |
0.8657 |
|
K+ (mEq/L) |
2.3 ± 0.3 (1.8−2.9) |
2.4 ± 0.3 (2.1−3.1) |
2.2 ± 0.3 (1.9−3.2) |
0.0798 |
|
Ca 2 + (mEq/L) |
1.11 ± 0.13 (0.80−1.30) |
1.12 ± 0.14 (0.92−1.44) |
1.09 ± 0.15 (0.76−1.32) |
0.7023 |
|
Cl − (mEq/L) |
110 ± 3 (106−115) |
111 ± 4 (104−119) |
112 ± 4 (107−120) |
0.0722 |
|
Hb (g/dL) |
11.5 ± 0.8 (9.5−12.6) |
11.6 ± 0.8 (10.0−13.0) |
9.3 ± 0.7 * † (7.3−10.8) |
< 0.0001 |
|
Lactate (mmol/L) |
0.8 ± 0.3 (0.5−1.8) |
0.6 ± 0.3 (0.3−1.2) |
0.7 ± 0.2 (0.4−1.3) |
0.2487 |
|
Mean arterial pressure (mmHg) |
94 ± 9 (76−103) |
86 ± 10 * (71−107) |
70 ± 10 * † (55−88) |
< 0.0001 |
Effects of the Alkaline Agents During Low-Flow ECCO2R on CO2 Inhalation Models
One rabbit in the NaHCO 3 group was excluded because of a failure of the ECCO 2 R system. The characteristics before administering the alkaline agents were not different among the three groups ( Supplemental Table 1 ). The data characteristics after 180-min treatment with alkaline agents are shown in Table 2 . Although RRs were not different between the three groups, MV in the trometamol group was lower than that of the saline group ( Fig. 2 ). Base excess, pH, and HCO 3 − in the NaHCO 3 and trometamol groups were higher than those in the saline group ( Fig. 3 ). Furthermore, base excess and HCO 3 − in the trometamol group were lower than those in the NaHCO 3 group. Na+ in the NaHCO 3 group was higher than that in the saline and trometamol groups. Cl− in the NaHCO 3 group was lower than that in the saline group. The anion gap in the trometamol groups was lower than those in the saline and NaHCO 3 groups.
Table 2. Characteristics of the saline, NaHCO3, and trometamol groupsa.
aValues are presented as mean ± standard deviation, with range in brackets.
bAnion gap = Na+ − Cl− − HCO3−
*significantly different in comparison with Saline, p < 0.05;
†significantly different in comparison with NaHCO3, p < 0.05.
BW: body weight.
|
Characteristic |
Saline (n = 5) |
NaHCO3 (n = 4) |
Trometamol (n = 5) |
p value |
|
Minute ventilation/BW (L/min/kg) |
0.556 ± 0.138 (0.380 − 0.752) |
0.451 ± 0.026 (0.428 − 0.477) |
0.381 ± 0.050* (0.299 − 0.432) |
0.0320 |
|
Respiratory rate (per min) |
47 ± 9 (38 − 59) |
48 ± 7 (39 − 53) |
44 ± 8 (38 − 58) |
0.7897 |
|
pH |
7.257 ± 0.032 (7.216 − 7.299) |
7.505 ± 0.020* (7.483 − 7.532) |
7.467 ± 0.028* (7.422 − 7.491) |
< 0.0001 |
|
PaCO2 (mmHg) |
42.9 ± 6.9 (38.7 − 55.1) |
51.6 ± 2.8 (48.8 − 54.6) |
44.7 ± 3.4 (40.7 − 48.5) |
0.0523 |
|
PaO2 (mmHg) |
224 ± 15 (206 − 243) |
202 ± 15 (180 − 211) |
201.2 ± 9.7* (190 − 216) |
0.0309 |
|
HCO3 − (mEq/L) |
18.5 ± 3.2 (16.1 − 23.9) |
40.6 ± 1.5* (39.5 − 42.7) |
31.4 ± 1.5*† (30.4 − 33.9) |
< 0.0001 |
|
Base excess (mEq/L) |
− 6.4 ± 5.4 ( − 10.4 − 2.8) |
15.6 ± 1.3* (14.4 − 17.2) |
7.2 ± 1.3*† (5.8 − 9.2) |
< 0.0001 |
|
Anion gap (mEq/L)b |
4.7 ± 2.4 (1.6 − 6.9) |
2.6 ± 2.0 (1.3 − 5.5) |
− 9.4 ± 2.3*† ( − 12.8 to − 6.5) |
< 0.0001 |
|
Na+ (mEq/L) |
138 ± 2 (136 − 142) |
149 ± 2* (147 − 151) |
133 ± 6† (128 − 143) |
0.0004 |
|
K+ (mEq/L) |
2.3 ± 0.4 (1.8 − 2.7) |
2.3 ± 0.3 (1.9 − 2.7) |
2.7 ± 0.2 (2.3 − 2.8) |
0.1779 |
|
Ca2+ (mEq/L) |
1.06 ± 0.15 (0.92 − 1.29) |
0.81 ± 0.04 (0.77 − 0.84) |
0.90 ± 0.19 (0.72 − 1.22) |
0.0628 |
|
Cl − (mEq/L) |
115 ± 3 (112 − 120) |
106 ± 3* (102 − 110) |
111 ± 5 (108 − 120) |
0.0131 |
|
Hb (g/dL) |
7.9 ± 0.7 (6.7 − 8.6) |
8.8 ± 0.5 (8.3 − 9.4) |
8.7 ± 0.6 (8.1 − 9.4) |
0.0727 |
|
Lactate (mmol/L) |
1.9 ± 1.2 (0.5 − 3.8) |
1.6 ± 0.6 (0.9 − 2.1) |
1.4 ± 0.4 (0.8 − 2.0) |
0.6998 |
|
Mean arterial pressure (mmHg) |
66 ± 13 (46 − 79) |
67 ± 9 (54 − 77) |
64 ± 10 (50 − 79) |
0.9618 |
Fig. 2 . Minute ventilation (MV) and respiratory rate after 30-min CO 2 inhalation, 30-min extracorporeal CO 2 removal (ECCO 2 R), and 180-min treatment with alkaline agents a .
a Data are expressed as mean ± standard deviation values.
* p < 0.05 in one-way analysis of variance, followed by Tukey’s honestly significant difference test for multiple post-hoc comparisons.
BW: body weight; NS: not significant; THAM: trometamol.
Fig. 3 . Atrial blood gas and electrolyte data after 30-min CO 2 inhalation, 30-min extracorporeal CO 2 removal (ECCO 2 R), and 180-min treatment with alkaline agents a .
a Data are expressed as mean ± standard deviation values.
* p < 0.05 in one-way analysis of variance, followed by Tukey’s honestly significant difference test for multiple post-hoc comparisons.
NS: not signifi cant
Blood gas data in the inflow and outflow of the ECCO 2 R circuits in the saline, NaHCO 3 , and trometamol groups are shown in Table 3 . The amounts of CO 2 removed are exhibited in Fig. 4 . The total amounts of CO 2 removed in the NaHCO 3 group were lower than those in the saline and trometamol groups ( Fig. 4 ).
Table 3 . Blood gas data in the inflow and outflow of the extracorporeal CO 2 removal (ECCO 2 R) circuits in the saline, NaHCO 3 , and trometamol groups a .
a Values are presented as mean ± standard deviation, with range in brackets.
*significantly different in comparison with Saline, p < 0.05;
†significantly different in comparison with NaHCO3 , p < 0.05
|
Parameters |
Saline (n = 5) |
NaHCO 3 (n = 4) |
Trometamol (n = 5) |
p value |
|
Outflow blood |
||||
|
pH |
7.221 ± 0.029 (7.176−7.245) |
7.494 ± 0.024 * (7.461−7.515) |
7.449 ± 0.026 * (7.401−7.469) |
< 0.0001 |
|
PaCO 2 (mmHg) |
52.9 ± 4.9 (48.0−59.8) |
55.8 ± 2.9 (53.0−59.3) |
49.9 ± 2.8 (47.0−54.4) |
0.1046 |
|
PaO 2 (mmHg) |
38.7 ± 8.7 (30.1−49.4) |
35.9 ± 2.1 (34.2−38.8) |
35.1 ± 5.5 (30.0−43.8) |
0.6607 |
|
HCO 3 − (mEq/L) |
20.9 ± 2.3 (19.3−25.0) |
42.5 ± 1.0 * (41.6−43.4) |
34.1 ± 2.9 * † (30.2−38.3) |
< 0.0001 |
|
SO 2 (%) |
54.2 ± 13.3 (40.0−69.6) |
72.6 ± 4.0 * (68.2−77.1) |
70.2 ± 2.8 (61.8−81.5) |
0.0262 |
|
Inflow blood |
||||
|
pH |
7.454 ± 0.101 (7.305−7.555) |
7.676 ± 0.078 * (7.605−7.748) |
7.596 ± 2.3 * (7.571−7.630) |
0.0031 |
|
PaCO 2 (mmHg) |
24.4 ± 5.3 (17.8−31.7) |
33.8 ± 6.9 (27.7−40.3) |
29.7 ± 4.1 (22.6−32.8) |
0.0691 |
|
PaO 2 (mmHg) |
623 ± 44 (575−688) |
570 ± 51 (499−616) |
588 ± 19 (559−604) |
0.1569 |
|
HCO 3 − (mEq/L) |
16.6 ± 1.5 (15.3−19.1) |
39.8 ± 0.5 * (39.1−40.4) |
28.9 ± 2.9 * † (24.1−31.9) |
< 0.0001 |
Fig. 4 . Amount of CO 2 removed during extracorporeal CO 2 removal (ECCO 2 R) and ECCO 2 R plus alkaline agents in CO 2 inhalation models a .
a Data are expressed as mean ± standard deviation values.
* p < 0.05 in one-way analysis of variance, followed by Tukey’s honestly significant difference test for multiple post-hoc comparisons.
ECMO: extra-corporeal membrane oxygenation; THAM: trometamol.
Discussion
The results of this study indicated that the attachment of the low-flow ECCO 2 R system reduced MV in subjects preserving spontaneous breathing efforts with CO 2 overload. The addition of NaHCO 3 improved acidemia but did not change MV. Meanwhile, the addition of trometamol improved acidemia and reduced MV. The total amounts of CO 2 removed during ECCO 2 R in the NaHCO 3 group were lower than those in the saline and trometamol groups.
Several studies have shown that ECMO with a larger blood flow inhibited spontaneous breathing. 5 , 6 However, ordinary ECMO required large catheters and was highly invasive to awake patients preserving spontaneous breathing. Alternatively, ECCO 2 R, which requires a low blood flow rate, is less invasive than ordinary ECMO. In particular, low-flow ECCO 2 R, which was performed by connecting an artificial lung to a renal replacement system using a thinner double-lumen catheter, is less invasive and can be performed easily. 10 A study has reported that protective ventilation with low VT could be achieved by ECCO 2 R. 17 Few studies have focused on whether low-flow ECCO 2 R is useful in suppressing strong spontaneous breathing efforts. In this study, low-flow ECCO 2 R effectively reduced ventilation volume and RR in CO 2 inhalation models preserving spontaneous breathing efforts.
In this study, mild metabolic acidosis was caused by diluting the saline primed in the ECCO 2 R circuit. 18 In a study, we showed that administration of alkaline agents had suppressive effects on spontaneous breathing efforts. 15 We investigated whether the administration of alkaline agents aiming at +10 of base excess suppressed spontaneous breathing efforts even during ECCO 2 R. The administration of trometamol was effective in correcting acidosis and reducing MV. However, the administration of NaHCO 3 was effective in correcting acidosis but could not mitigate MV. The CO 2 generated by the NaHCO 3 offset the amount of CO 2 removed by ECCO 2 R to reduce the effects of ECCO 2 R. Problems, such as Ca precipitation, were encountered when removing CO 2 made the blood pH high at the outflow of ECCO 2 R. The blood pH at the outflow of ECCO 2 R defines the limit of CO 2 removal. In such cases, using trometamol rather than NaHCO 3 is better. Acidemia is often a problem when the patient wears or withdraws from ECMO. Temporary administration of trometamol may be helpful as renal compensation usually takes time.
In conclusion, the attachment of low-flow ECCO 2 R reduced MV in subjects preserving spontaneous breathing effort with CO 2 overload. The addition of NaHCO 3 improved acidemia but did not change MV, whereas the addition of trometamol improved acidemia and reduced MV.
Acknowledgments
This work was supported by Grant-in-Aid for Scientific Research (C) from the Japan Society for the Promotion of Science (No. 15K10535).
Conflict of Interest
No potential conflicts of interest exist.
Supplemental Table 1 . Supplemental Table 1. Characteristics before the administration of the alkaline agentsa.
aData are expressed as mean ± standard deviation values.
bAnion gap = Na+ − Cl− − HCO3−.
|
Characteristic |
Saline (n = 5) |
NaHCO 3 (n = 4) |
Trometamol (n = 5) |
p value |
|
Minute ventilation/BW (L/min/kg) |
0.557 ± 0.134 |
0.503 ± 0.050 |
0.600 ± 0.088 |
0.383 |
|
Respiratory rate (min) |
52 ± 11 |
42 ± 7 |
55 ± 16 |
0.337 |
|
pH |
7.347 ± 0.055 |
7.319 ± 0.056 |
7.374 ± 0.024 |
0.260 |
|
PaCO 2 (mmHg) |
41.4 ± 6.5 |
41.0 ± 3.9 |
37.7 ± 3.2 |
0.458 |
|
PaO 2 (mmHg) |
210.2 ± 12.7 |
200.0 ± 17.0 |
202.8 ± 16.1 |
0.589 |
|
HCO 3 − (mEq/L) |
22.2 ± 3.9 |
20.0 ± 1.2 |
21.5 ± 1.8 |
0.477 |
|
Base excess (mEq/L) |
−2.8 ± 4.0 |
−4.8 ± 2.2 |
−2.9 ± 1.8 |
0.524 |
|
Anion gap (mEq/L) b |
3.2 ± 1.6 |
6.3 ± 3.2 |
4.5 ± 1.2 |
0.269 |
|
Na+ (mEq/L) |
137 ± 5 |
139 ± 1 |
138 ± 3 |
0.744 |
|
K+ (mEq/L) |
2.3 ± 0.5 |
2.1 ± 0.2 |
2.2 ± 0.2 |
0.705 |
|
Ca 2 + (mEq/L) |
1.06 ± 0.23 |
1.07 ± 0.10 |
1.08 ± 0.07 |
0.969 |
|
Cl − (mEq/L) |
112 ± 3 |
113 ± 2 |
112 ± 5 |
0.905 |
|
Hb (g/dL) |
8.8 ± 0.8 |
9.5 ± 0.4 |
9.4 ± 0.4 |
0.179 |
|
Lactate (mmol/L) |
0.7 ± 0.2 |
0.8 ± 0.2 |
0.8 ± 0.3 |
0.643 |
|
Mean arterial pressure (mmHg) |
69 ± 11 |
65 ± 8 |
77 ± 10 |
0.398 |
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