Study Selection
The searches yielded a total of 3442 citations. After excluding duplicates and reviewing titles and abstracts, 16 studies were left for full-text assessment. From those, 4 were excluded because they did not present any outcome of interest. Finally, 12 studies were included in this systematic review, as demonstrated in Figure 1.
Studies Characteristics
Of the 12 included studies, four were conducted in Germany, two in Egypt, and one in each of the following countries: France, Switzerland, United States, Croatia, India and Japan. A total number of 1419 patients were assessed in this systematic review, including all types of intervention and comparisons. Table 1 demonstrates a summary of the characteristics of the studies, including age, gender, levels of creatinine and urea, as well as disease severity classification systems such as APACHE, SAPS, SOFA and TISS.
Risk of bias
Most of the studies presented unclear risk of bias in relation to the assessed item. From the 12 included studies, seven presented unclear risk of bias in relation to random sequence generation, and 9 in relation to allocation concealment, which means there was insufficient information to permit judgement of ‘Low risk’ or ‘High risk’. In most cases, the studies did not mention the methods used for random sequence generation and allocation concealment.. Therefore, 10 of the 12 studies were considered of unclear risk of selection bias. Only one study described outcome assessment as blinded and was considered of low risk of bias.
In relation to attrition bias, eight of the 12 included studies present low risk of bias, since no missing data were identified, nor did this appear to be related to the true outcome. The other four studies presented unclear risk of bias since there was insufficient reporting of attrition/exclusions to permit judgement. Risk of bias related to selective reporting was also unclear. None of the 12 studies referred a source where the study protocol could be assessed by readers, such as clinicaltrials.gov. Although the outcomes presented in the studies appear coherent with the respective study aims, it was not possible to exclude bias related to selective outcome reporting. Table 2 summarizes the assessment of risk of bias of included studies.
Comparison of hemodynamic parameters
Heart Rate
Two [14,19] of the six trials comparing intermittent versus continuous modalities of RRT evaluated differences in heart rate between the modalities. Schefold et al (2014) [14] did not identify any differences between the groups when assessing heart rate from day 1 to day 21 after treatment. John et al (2001) [19] reported that CVVH group heart rate declined after 1 and 4 hours in comparison with IHD group. However, after 24h, heart rate had returned to baseline in the IHD group and the difference between both groups was no longer observed.
When comparing hybrid versus continuous modalities, two [20,22] of the three studies reported heart rate comparisons. None of the studies found differences in heart rate up to 24 days after intervention. Similarly, a study by Badawy et al (2012) [24] comparing furosemide versus CVVHDF did not find differences between the groups in relation to heart rate, up to 72 hours after starting treatment. Table 3 summarizes data on heart rate comparisons from the included studies.
Blood pressure and hypotensive episodes
When comparing intermittent versus continuous modalities of RRT, four [14,16,17,19] of the six studies reported blood pressure comparisons between the groups. John et al (2001) [19] observed an increase in systolic blood pressure after 0.5 and 2h of CVVH in contrast with IHD. However, this difference was not observed after 24 hours of interventions. The other studies did not find differences between the groups in relation to blood pressure. A study by Nand et al (2010) [23], which compared CAVHDF to CVVHDF, observed an increase in MAP in both groups, 24 hours after starting the treatments. None of the patients developed hypotension secondary to the procedures.
The incidence of hypotensive episodes varied from 5 to 60% among the included studies, but did not differ according to RRT modality were observed. Table 3 summarizes the data on blood pressure and hypotensive episode comparisons between the groups reported in the included studies.
Use of catecholamines
In relation to the use of catecholamines, included studies presented distinct results. Among the studies comparing intermittent versus continuous modalities of RRT, Uehlinger et al (2005) [16] reported doses significant higher of Dobutamine in patients from the CVVHDF group, when compared to IHD. The same difference was not observed when evaluated doses of Adrenaline, Noradrenaline, and Dopamine. The other three studies [14,17,19] comparing the use of catecholamines between intermittent versus continuous modalities of RRT did not find any differences between the groups. The same was observed among the other comparisons. Table 3 summarizes the results on use of catecholamines in the included studies.
Impact of hemodynamic parameters on clinical outcomes
Included studies compared hemodynamic parameters among different types of RRT; however, most of them did not assess the impact of these changes on clinical outcomes such as morbidity and mortality, except the studies from Augustine et al (2004) [17] and Uehlinger et al (2005) [16].
In Augustine et al (2004) study [17], a trial comparing IHD versus CVVHDF which included 40 patients in each group, the authors reported that, in univariate analysis, lower values of baseline MAP, greater MAP variation during dialysis, increased use of pressors at baseline and during dialysis were related to decreased survival time, hazard ratio (HR) 0.97 (95% CI, 0.95 to 1.00; P = 0.036); HR 1.04 (95% CI, 1.01 to 1.08; P = 0.032); HR 1.47 (95% CI, 1.19 to 1.82; P<0.001); HR 1.91 (95% IC, 1.07 to 3.41; P = 0.028); respectively. When multivariate analysis was conducted, greater MAP variation during dialysis and increased use of pressors at baseline were associated with shorter survival times. The authors reported that for each 1 mmHg of MAP variation during dialysis, the HR was 1.06 (95% CI, 1.02 to 1.11; P = 0.005) [17].
Besides that, mean MAP variation on dialysis was 1.7±7.1 mmHg during initial dialysis in patients who did not recover renal function compared to - 4.5±5.4 mm Hg in patients who recovered renal function (P = 0.01). In patients with renal recovery, this represented a significant increase in MAP on dialysis versus baseline (P = 0.03). Renal recovery did not correlate with baseline MAP, number of baseline pressors, or increased pressor dose on dialysis therapy. Logistic regression analysis demonstrated that a greater MAP variation on dialysis negatively correlated with renal recovery, OR 0.81 (95% CI, 0.68 to 0.95; P = 0.01) [17].
Uehlinger et al (2005) [16], in their trial comparing 55 patients undergoing IHD to 70 patients undergoing CVVHDF, demonstrated that treatment with catecholamines was a strong predictor of mortality, OR 4.3 (P = 0.002) [16].