This trial aimed to compare the dialysis complications occurring during different durations of extended daily dialysis (EDD) sessions in critically ill AKI patients. We included patients older than 18 years with AKI associated with sepsis admitted to the intensive care unit and using noradrenaline dose ranging from 0.3 to 0.7
The high mortality rate among critically ill acute kidney injury (AKI) patients remains an unsolved problem in intensive care units (ICU) in spite of the considerable technological progress in renal replacement therapy (RRT) [
There is no consensus in the literature on the best dialysis method; intermittent haemodialysis (IHD) and continuous renal replacement therapies (CRRT) have been used in AKI [
There are few studies in the literature on EDD in AKI patients and they involve a small number of patients [
This is a prospective randomised clinical trial conducted from January 2012 to June 2013 in patients enrolled in the Brazilian University Hospital. The protocol was approved by the Institutional Ethical Committee. Written informed consent was obtained from patients or their next of kin. Patients were eligible for enrolment if they were 18 years of age or older, with AKI associated with sepsis and on a noradrenaline dose ranging from 0.3 to 0.7
Exclusion criteria were severe chronic kidney disease (basal creatinine higher than 4 mg/dL), previous chronic dialysis, kidney transplantation, and noradrenaline dose higher than 0.7
The indications for dialysis were uraemic symptoms, BUN level > 100 mg/dL (azotaemia), volume overload, electrolyte imbalance (potassium > 6 mEq/L after clinical treatment), or acid-base refractory disturbances (bicarbonate < 10 mEq/L after reposition). A patient was considered for enrolment if the judgment of the treating nephrologists was that he or she required dialysis and the mean arterial blood pressure (BP) was higher than 80 mm Hg, with a noradrenaline dose lower than 0.7
Patients were divided into two groups randomly, according to prescribed treatment time. Randomization was performed using sealed envelopes: group 1 (G1), patients undergoing EDD sessions lasting 6 hours, group 2 (G2), patients undergoing EDD sessions lasting 10 hours.
Dialysis was interrupted when there was partial renal function recovery (dialysis-independent) defined as restoration of urine output higher than 1000 mL/24 h associated with a progressive fall in serum values for creatinine (<4 mg/100 mL) and BUN (<50 mg/dL), a need to change dialysis method because of infectious, mechanical, or haemodynamic complications, more than 30 days of follow-up, or death.
The EDD session lasted 6 or 10 hours according to randomisation and, for practical reasons, it was decided that EDD would be carried out 6 days a week (Monday–Saturday). Dialysis nurses and dialysis technical nursing were responsible for EDD and operated the dialysis machines throughout the treatment. A double lumen catheter for central venous access (jugular, subclavian, or femoral vein, depending on the ease of access) was inserted blindly at the bedside by nephrologists, under local anaesthesia. An HD machine with volumetric control (
Anticoagulation was achieved with unfractionated heparin (usually a 1000 U bolus followed by 500 U/h) or saline flushes of 100 mL given every 30 min if anticoagulation was contraindicated. If EDD was interrupted for procedures, it was restarted later, attempting to complete 6 or 10 h of treatment. UF was prescribed during dialysis treatment as per the daily requirements. UF was performed at 300 mL/h to 500 mL/h and adjusted according to the alteration in haemodynamic parameters and fluid status of individual patients.
Bicarbonate (26 to 35 mEq/L), potassium (2 or 3 mEq/L), and sodium dialysate concentrations (142–148 mEq/L) were adjusted according to individual requirements. Dialysate temperature was low (35.5°C) to prevent hypotension.
During the procedures, BP monitoring was performed every 30 min. Hypotension was defined as a single systolic BP of less than 90 mm Hg or a mean arterial pressure (MAP) of less than 60 mm Hg. To treat a hypotension episode during EDD, protocols were applied involving the infusion of saline, discontinuation of UF, and an increased dose of vasoactive drugs, according to the clinical condition and fluid status of the patient. If, despite the measures above, haemodynamic instability persisted, posing risks to the patient, the therapy was discontinued.
Filter clotting was diagnosed as the presence of blood clots in the circuit, composed of dialyser and lines, which prevented the continuation of therapy. Hypokalaemia and hypophosphataemia were considered postdialysis complications, characterised by serum levels below 3.5 mEq/L and 3.5 mg/dL, respectively.
Treatment duration, episodes of filter clotting and replacement, vasoactive drug dose, and UF rate were recorded at the end of each session. Posttreatment BUN levels were measured by the slow flow method (with blood pump speed reduced to 50 mL/min). Blood samples were obtained from the arterial sampling port before the blood reached the dialyser. HD adequacy was determined by using urea kinetic modelling based on Kt/V [
The sample size calculation was based on the assumption that the overall hypotension would be 50% and that a difference of 20% in hypotension between patients undergoing sessions lasting 10 and 6 hours had to be detected to be clinically relevant. With a first-order error of 5% and a power of 80% a sample size of 59 sessions was needed in each treatment group.
Data analysis was performed using SAS for Windows (version 9.2: SAS Institute, Cary, NC, USA, 2012). All analyses were performed according to the intention-to-treat principle. Variables with normal distribution are described using means ± standard deviation; variables with a nonnormal distribution are described using medians and interquartile ranges.
During the study period (January 2012 to June 2013), a total of 203 patients were treated by dialysis: 101 by EDD (49.6%), 45 by conventional IHD (22%), 14 by CRRT (6.9%), and 43 by high-volume peritoneal dialysis (PD; 21.1%). The modality chosen was based on patients’ haemodynamic instability. PD was indicated when there was no contraindication for its use (recent abdominal surgery, multiple abdominal surgeries, severe hyperkalaemia with electrocardiogram changes, severe respiratory failure (FiO2 < 70%), and severe fluid overload). Conventional IHD was indicated for haemodynamically stable patients (without vasoactive drug use). EDD was indicated when patients were using a noradrenaline dose lower than 0.7
Inclusion of patients enrolled in the study.
The age was
Clinical characteristics of AKI patients treated with EDD.
Parameters |
|
---|---|
Age (years) |
|
Male gender |
53 (70.6) |
Weight (kg) |
|
Focus of infection |
|
Abdominal | 32 (42.6) |
Pulmonary | 25 (33.3) |
Others | 18 (24) |
Comorbidities |
|
Hypertension | 37 (49.3) |
DM | 15 (20) |
CKD | 9 (12) |
Heart failure | 41 (54.6%) |
ATN-ISS |
|
SOFA |
|
Dialysis complications |
|
Hypotension | 62 (82.6) |
Filter clotting | 19 (25.3) |
Hypokalemia | 8 (10.6) |
Hypophosphatemia | 15 (20) |
Patient outcome |
|
Recovery of renal function | 10 (13.5) |
Chronic dialysis | 6 (8.1) |
Death | 58 (78.3) |
Amounts shown in frequency, mean, standard deviation, and proportion.
AKI: acute kidney injury, EDD: extended daily dialysis, SAH: systemic arterial hypertension, DM: diabetes mellitus, CKD: chronic kidney diseases, ATN-ISS: prognostic specific to the NTA, and SOFA: sequential organ failure assessment score.
G1 consisted of 38 patients treated with 100 sessions, whereas G2 consisted of 37 patients treated with 95 sessions. Comparison of the clinical characteristics showed that G1 and G2 were similar in male predominance (65.7% versus 75.6%, resp.,
Clinical characteristics of AKI patients treated with different durations of EDD.
Parameters | G1 = 6 h ( |
G2 = 10 h ( |
|
---|---|---|---|
Age (years) |
|
|
0.28 |
Male gender |
25 (65.7) | 28 (75.6) | 0.34 |
Weight (kg) |
|
|
0.59 |
Infection site |
|||
Abdominal | 13 (34.2) | 12 (32.4) | 0.88 |
Pulmonary | 12 (31.5) | 20 (54.0) | 0.002 |
Comorbidities |
|||
Hypertension | 21 (55.2) | 16 (43.2) | 0.29 |
Heart failure | 20 (52.6) | 21 (56.8) | 0.41 |
DM | 8 (21) | 7 (18.9) | 0.81 |
CKD | 6 (15.7) | 3 (8.1) | 0.47 |
ATN-ISS |
|
|
0.47 |
SOFA |
|
|
0.20 |
Patient outcome |
|||
Recovery of renal function | 4 (10.5) | 6 (16.6) | 0.21 |
Chronic dialysis | 4 (10.5) | 2 (5.5) | 0.28 |
Death | 30 (78.9) | 28 (77.7) | 0.86 |
Amounts shown in frequency, mean, standard deviation, and proportion.
AKI: acute kidney injury, EDD: extended daily dialysis, SAH: systemic arterial hypertension, DM: diabetes mellitus, CKD: chronic kidney diseases, ATN-ISS: prognostic specific to the NTA, and SOFA: sequential organ failure assessment score.
Table
Dialysis complications of AKI patients treated with different durations of EDD.
Complications |
G1 = 6 h ( |
G2 = 10 h ( |
|
---|---|---|---|
Hypotension | 31 (81.5) | 31 (83.7) | 0.80 |
Filter clotting | 9 (23.6) | 10 (27) | 0.73 |
Hypokalemia | 5 (13.1) | 3 (8.1) | 0.71 |
Hypophosphatemia | 7 (18.4) | 8 (21.6) | 0.72 |
Amounts shown in proportion.
AKI: acute kidney injury, EDD: extended daily dialysis.
When dialysis complications were analysed by session, hypotension was present in 116 sessions (59.5%), while filter clotting was present in 29 sessions (14.9%). An increased noradrenaline dose was needed in 85.2% of the sessions and 19.1% of the sessions were interrupted. However, the group treated with sessions of 10 hours showed higher refractory to clinical measures for hypotension and dialysis sessions were interrupted more often (9.5 versus 30.1%,
Distribution of intradialytic complications by sessions of EDD according to different duration of sessions.
Complications |
G1 = 6 h ( |
G2 = 10 h ( |
|
---|---|---|---|
Hypotension | 63 (63%) | 53 (55.8%) | 0.21 |
Filter clotting | 11 (11%) | 18 (18.9%) | 0.72 |
Effective duration of dialysis | 5 h 46 min | 8 h 48 min | 0.021 |
Amounts shown in proportion.
EDD: extended daily dialysis.
The metabolic and fluid control of AKI patients treated with EDD lasting 6 and 10 hours are shown in Table
Metabolic and fluid control of the groups in the first three sessions of EDD.
G1 = 6 h ( |
G2 = 10 h ( |
|
|||||
---|---|---|---|---|---|---|---|
S1 ( |
S2 ( |
S3 ( |
S1 ( |
S2 ( |
S3 ( | ||
BUN (mg/dL) | 159 ± 60 | 120 ± 50 | 105 ± 38 | 152 ± 69a | 94 ± 38b | 96 ± 37c | NS |
BUN post (mg/dL) | 64 ± 32 | 47 ± 17 | 44 ± 20 | 48 ± 25a | 43 ± 20b | 41 ± 22c | NS |
URR | 0.61 ± 0.1 | 0.59 ± 0.1 | 0.62 ± 0.1 | 0.68 ± 0.1a | 0.64 ± 0.1b | 0.69 ± 0.1c | NS |
Kt/V | 1.09 ± 0.24 | 1.07 ± 0.25 | 1.09 ± 0.25 | 1.26 ± 0.26a | 1.21 ± 0.24b | 1.28 ± 0.27c | NS |
Cr (mg/dL) | 3.8 ± 1.4 | 3.2 ± 1.3 | 2.8 ± 1.2 | 3.7 ± 1.3a | 2.7 ± 0.8b | 2.5 ± 0.6c | NS |
K (mEq/L) | 4.4 ± 0.8 | 4.6 ± 1 | 4.4 ± 0.9 | 4.7 ± 1a | 4.2 ± 0.6b | 4 ± 0.5c | NS |
Bic (mEq/L) | 17 ± 3 | 18.7 ± 3 | 19.9 ± 3.9 | 18.6 ± 4.2a | 19.7 ± 7.3b | 21 ± 2.5c | NS |
pH | 7.2 ± 0.09 | 7.2 ± 0.1 | 7.2 ± 0.09 | 7.2 ± 0.1a | 7.3 ± 0.1b | 7.3 ± 0.09c | NS |
Presc UF (mL) | 1957 ± 933 | 2182 ± 857 | 2260 ± 812 | 2524 ± 916a | 2766 ± 992b | 2611 ± 977c | NS |
Actual UF (mL) | 1731 ± 818 | 1967 ± 980 | 2146 ± 820 | 2332 ± 947a | 2214 ± 1440b | 2376 ± 1243c | NS |
UF rate (mL/h) | 288.5 ± 136 | 327 ± 163 | 357 ± 136 | 233 ± 94d | 221 ± 144e | 237 ± 124f | <0.05 |
Fluid balance (mL) | −401 ± 181 | −690 ± 40 | −731 ± 125 | −396 ± 47a | −614 ± 140b | −652 ± 141c | NS |
Amounts shown in mean and standard deviation.
EDD: extended daily dialysis.
BUN: blood urea nitrogen, Cr: creatinine, URR: rate reduction of urea, K: potassium, Bic: bicarbonate, and presc UF: prescribed ultrafiltration.
aSimilar to S1 of G1.
bSimilar to S2 of G1.
cSimilar to S3 of G1.
dDifferent from S1 of G1.
eDifferent from S2 of G1.
fDifferent from S3 of G1.
NS: not significant (
Initial and final dose of vasoactive drugs and blood pressure according to the different duration of sessions.
G1 = 6 h ( |
G2 = 10 h ( |
|
|||||
---|---|---|---|---|---|---|---|
S1 ( |
S2 ( |
S3 ( |
S1 ( |
S2 ( |
S3 ( | ||
Initial VAD | 0.55 ± 0.5d | 0.68 ± 0.6d | 0.52 ± 0.3d | 0.53 ± 0.2a,d | 0.59 ± 0.4b,d | 0.61 ± 0.4c,d | NS |
Final VAD | 0.70 ± 0.5 | 0.78 ± 0.7 | 0.64 ± 0.5 | 0.74 ± 0.4a | 0.75 ± 0.6b | 0.70 ± 0.5c | NS |
SBP start | 118 ± 23e | 128 ± 28e | 113 ± 27e | 128 ± 23a,e | 114 ± 29b,e | 128 ± 26c,e | NS |
DBP start | 67 ± 16f | 64 ± 16f | 56 ± 14f | 68 ± 15a,f | 64 ± 18b,f | 68 ± 13c,f | NS |
SBP end | 114 ± 26 | 121 ± 27 | 136 ± 13 | 124 ± 22a | 133 ± 23b | 123 ± 17c | NS |
DBP end | 63 ± 16 | 65 ± 15 | 69 ± 17 | 68 ± 15a | 73 ± 15b | 67 ± 9c | NS |
Amounts shown in mean and standard deviation.
VAD: vasoactive drug, EDD: extended daily dialysis, SBP: systolic blood pressure, and DBP: diastolic blood pressure.
aSimilar to S1 of G1.
bSimilar to S2 of G1.
cSimilar to S3 of G1.
dDifferent from VAD end,
eDifferent from SBP end,
fDifferent from DBP end,
NS: not significant (
Table
Distribution of episodes of intradialytic complications according to sessions and groups.
Session | Hypotension (%) |
|
Filter clotting (%) |
|
||
---|---|---|---|---|---|---|
G1 ( |
G2 ( |
G1 ( |
G2 ( | |||
S1 | 36.5a,c | 37.7b | 1.0 | 45.4b | 33.3a,c | 0.7 |
S2 | 26.9d | 18.8d | 0.4 | 9.0d | 22.2d | 0.6 |
S3 | 17.4 | 20.7 | 0.8 | 9.0 | 16.6 | 0.9 |
Amounts shown in proportion.
aSimilar to S2,
bDifferent from S2 and S3,
cDifferent from S3,
dSimilar to S3,
This clinical trial evaluated and compared intra- and postdialysis complications in critically ill AKI patients undergoing EDD sessions of different durations (6 versus 10 h). There are few studies on EDD in AKI patients and most of them included a small number of patients or are review articles, and none of them compared dialysis complications of EDD sessions of different durations [
Hypotension is the main dialysis complication in critically ill AKI patients and it may occur in over 20% of patients [
To solve the problem of hypotension during EDD sessions, protocols including saline infusion, the discontinuation of UF, and an increase in noradrenaline dose were applied, according to the clinical condition of the patient and fluid status. If, despite the above measures, the instability of haemodynamics persisted, posing risks to the patient, the therapy was discontinued, which occurred in 22 sessions (19.1%).
The results of previous prospective investigations are controversial and hypotension during EDD sessions prevalence ranges from 0 to 50% [
In our study, the final noradrenaline dose was higher than the initial dose, suggesting that BP was kept stable due to the increase in noradrenaline dose. However, previous smaller prospective investigations showed that EDD was very well tolerated [
The two groups were similar in hypotension and increase in noradrenaline dose. We believe it happened because the group treated with sessions of 10 hours showed higher refractory to clinical measures for hypotension and dialysis sessions were interrupted more often (9.5 versus 30.1%,
The results of this study indicate a higher prevalence of hypotension than that reported in the literature [
Filter clotting is another important intradialysis complication. It involves treatment interruption and blood loss from the patient, which may contribute to the haemodynamic instability. It is characterised by staining blood extremely dark shadows or black striations in the capillary, with changes in venous and transmembrane pressures [
Berbece and Richardson [
When we evaluated intradialysis complications in the first three EDD sessions, we observed that these complications were more frequent in the first session, and, after, they became less frequent. Doshi and Murray [
Postdialysis complications were less frequent than intradialysis complications and there was no difference between the two groups regarding postdialysis complications. Hypokalaemia and hypophosphataemia occurred in 10.6 and 20% of patients, respectively. There are few studies comparing these complications after dialysis, with which to compare our results. Marshall et al. [
Metabolic control and fluid status were similar in the groups treated with 6 h versus 10 h EDD sessions. The BUN and creatinine levels were higher in the first session in both groups and stabilised thereafter. URR was constant, around 0.6 in both groups, while delivered Kt/V was close to 1.0, actual UF remained around 2000 mL per session, without exceeding 500 mL/h and fluid balance was kept around −600 mL in both groups. Similar results have been reported in the literature. Fieghen et al. [
Comparative study of intensive EDD (serum urea levels greater than or equal to 15 mmol/L) and standard EDD (serum urea levels between 20 and 25 mmol/L) did not show a difference in patient survival or recovery of renal function [
Previous studies showed weekly Kt/V values for EDD of between 5.8 and 8.4 [
However, there is a limitation of Kt/V as a marker of efficacy for this treatment method. A study by Eloot et al. [
Concerning patient outcome, 13.5% of patients presented renal function recovery, 8.1% of patients remained on dialysis after 30 days, and 78.4% of patients died. In this study, the mortality rate was higher than that related to previous American and European studies, which showed an in-hospital mortality rate of AKI patients treated with EDD of 50 to 62% [
Our study has several limitations. First, the small number of patients studied and the single-centre design weaken the comparison between mortality and recovery of kidney function, and the exclusion of the sickest patients (17 patients receiving a noradrenaline dose higher than 0.7
Our results showed that intra- and postdialysis complications were similar between the groups treated with EDD lasting 6 versus 10 h and that the group treated with sessions of 10 hours showed higher refractory to clinical measures for hypotension and dialysis sessions were interrupted more often, with no benefit in treating AKI patients with more prolonged sessions. The findings of our study suggest that EDD lasting 6 or 10 h may provide adequate treatment for most AKI patients, achieving adequate metabolic control and net UF. However, hypotension was the most frequent complication with sessions of this dialysis method lasting 6 or 10 h and it certainly did not contribute to renal (or cardiac, brain, or gut) functional recovery. Due to the severe haemodynamic instability of the AKI patients in the present study, we questioned whether CRRT would not be the most appropriate therapy. Finally, larger studies in this area are needed to clarify the impact of EDD on patient survival and recovery of kidney function.
The authors declare that there is no conflict of interests regarding the publication of this paper.