Current protocols using pre/post hydration with Bicarbonate 1.4% IV or NaCl 0.9% IV are functioning well in practice. However, it is necessary to compare the recommended hydration protocols for patients with impaired renal function in the guideline to newly published approaches and evaluate if the recommendations have to be updated. In addition, an investigation of the possibility to adapt protocols for specific situations in interventional radiology or cardiology, and tailor prehydration dependent on the route of CM administration (intravenous or intra-arterial with second pass renal exposure vs. intra-arterial with first pass renal exposure) is required.

In the current module, the following possible strategies are compared:

1. Hydration versus no hydration
2. Sodium chloride (NaCl) versus sodium bicarbonate (NaHCO3) hydration
3. Pre-hydration only versus pre- and posthydration
4. Oral versus intravenous hydration
5. Hydration with controlled diuresis

Table 3. Summary of Findings

Population: Patients with impaired renal function (chronic kidney disease, chronic renal failure, CKD stage 3 or higher, eGFR <60 ml/min/1.73m²) undergoing radiological or cardiological examinations with iodine-containing contrast media.

Intervention: Hydration

Comparator: No hydration

Click here to see this table in a document

_{^1. Inconsistency: serious. Due to conflicting results and differences in the type of hydration.}

_{Imprecision: very serious. Due to overlap of the lower and upper limit of the 95% confidence interval with the minimal clinically important difference.}

_{^2. Inconsistency: serious. Due to differences in the type of hydration.}

_{Imprecision: very serious. Due to no events occurred and the optimal information size was not achieved.}

_{^3. Risk of bias: serious. Due to lack of blinding.}

_{Imprecision: very serious. Due to overlap of the lower and upper limit of the 95% confidence interval with the minimal clinically important difference.}

_{^4. Risk of bias: serious. Due to loss to follow-up}

_{Imprecision: very serious. Due to overlap of the lower and upper limit of the 95% confidence interval with the minimal clinically important difference.}

_{^5. Risk of bias: serious. Due to lack of blinding.}

_{Inconsistency: serious. Due to conflicting results and differences in the type of hydration.
Imprecision: serious. Due to the low number of events.}

Table 6. Summary of Findings

Population: Patients with impaired renal function (chronic kidney disease, chronic renal failure, CKD stage 3 or higher, eGFR <60 ml/min/1.73m²) undergoing radiological or cardiological examinations with iodine-containing contrast media.

Intervention: NaCl

Comparator: NaHCO3

Click here to see this table in a document

_{^1. Inconsistency: serious. Due to conflicting results and heterogeneity
Imprecision: very serious. Due to overlap of the upper and lower limit of the 95% confidence interval with the minimal clinically important difference}

_{^2. Indirectness: serious. Due to differences in the hydration type (pre- versus pre- and posthydration)}

_{Imprecision: very serious. Due to overlap of the upper and lower limit of the 95% confidence interval with the minimal clinically important difference}

_{^3. Inconsistency: serious. Due to conflicting results and heterogeneity}

_{Imprecision: very serious. Due to the optimal information size which was not achieved and the low number of events}

_{^4. Imprecision: very serious. Due to overlap of the upper and lower limit of the 95% confidence interval with the minimal clinically important difference and the optimal information size was not achieved.}

_{^5. Inconsistency: serious. Due to heterogeneity between the studies}

_{Imprecision: very serious. Due to the optimal information size which was not achieved and the low number of events}

_{^6. Inconsistency: serious. Due to differences in the hydration type (pre- versus pre- and posthydration)}

_{Imprecision: very serious. Due to the optimal information size which was not achieved and the low number of events}

Table 8. Summary of Findings

Population: Patients with impaired renal function (chronic kidney disease, chronic renal failure, CKD stage 3 or higher, eGFR <60 ml/min/1.73m²) undergoing radiological or cardiological examinations with iodine-containing contrast media.

Intervention: Prehydration

Comparator: Pre- and posthydration

Click here to see this table in a document

_{^1. Indirectness: serious. Due to differences in the hydration type used for pre- and posthydration}

_{Imprecision: very serious. Due to overlap of the upper and lower limit of the 95% confidence interval with the minimal clinically important difference}

_{^2. Indirectness: serious. Due to differences in the hydration type used for pre- and posthydration}

_{Imprecision: very serious. Due to no events occurred and the optimal information size which was not achieved}

Question 1-3 update 2025.

Question 1: hydration versus no hydration

Description of studies

A total of four studies were included in the analysis of the literature. Three RCTs were found in the search of 2017 and two studies were added in 2025. Important study characteristics and results are summarized in table 2. The assessment of the risk of bias is summarized in the risk of bias tables (under the tab ‘Evidence tabellen’).

Chen (2008) performed a prospective, randomized, parallel-group, open label study in three centers in China to study the effect of pre- and posthydration with 0.45% saline on major clinical endpoints after 6 months and the incidence of PC-AKI after elective PCI. They studied all consecutive patients with myocardial ischemia scheduled for elective PCI, divided into a group of 660 patients (mean age 60±8 years) with normal or mildly impaired renal function (creatinine <133, mean 114±26 umol/l and eGFR 53±16 ml/min/1.73m²) and a group of 276 patients (mean age 63±11 years) with moderate to severely impaired renal function (creatinine >133; mean creatinine 220±9 umol/l and eGFR 28±2 ml/min/1.73m²). Patients were excluded if (1) the coronary anatomy not suitable for PCI; (2) emergency coronary artery bypass grafting (CABG) being required; (3) patients in chronic peritoneal or hemodialytic treatment; (4) acute myocardial infarction (AMI) at admission. In both groups, hydration was given with hypotonic NaCl 0.45% at a rate of 1 ml/kg/min for 12 hours before and 6 hours after PCI. In patients with reduced left ventricular function (ejection fraction <40%), infusion rate was reduced to 0.8 ml/kg/min. Only in the group with moderate to severely impaired renal function, all patients received a loading dose of 1200 mg N-Acetyl Cysteine 12 hours before PCI. Primary endpoint consisted of clinical driven revascularization (either PCI or CABG), death from all causes and requiring emergency renal-replacement therapy during the 6 months follow-up. They further studied adverse events such as acute pulmonary edema during 6 months follow-up and the incidence of PC-AKI defined as an absolute increase of serum creatinine >44 umol/L at 48 hours after PCI in the two groups.

Kooiman (2014) described 138 patients with eGFR <60 ml/min/1.73m² undergoing chest CT for suspected pulmonary embolism. Sixty-seven patients received no hydration, and the remaining 71 patients received 250ml NaHCO3 1.4% within one hour prior to CT.

Nijssen (2017) performed a prospective, randomised, phase 3, single centre, parallel-group, open-label, non-inferiority trial (AMACING) in the Netherlands to determine whether giving no prophylaxis is non-inferior to standard care prophylactic hydration. Patients aged 18 years and older (mean age 72±9 years) who received an elective procedure requiring intravascular iodinated contrast material with known eGFR lower than 60 mL per min/1.73m² were eligible. Inclusion criteria were patients with an eGFR between 45 and 59 mL per min/1.73 m² combined with either diabetes, or at least two predefined risk factors (age >75 years; anaemia defined as haematocrit values <0.39 L/L for men, and <0.36 L/L for women; cardiovascular disease; non-steroidal anti-inflammatory drug or diuretic nephrotoxic medication); or eGFR between 30 and 45 mL per min/1.73 m²; or multiple myeloma or lymphoplasmacytic lymphoma with small chain proteinuria. In total, 328 patients received hydration with 0.9% NaCl (52% short protocol and 48% long protocol of respectively 4 hours and 12 hours before and after contrast) and 332 patients received no hydration. Groups were comparable at baseline. Mean eGFR was 47±8 ml/min/1.73m² and 35% had an eGFR 30-45 ml/min/1.73m². 48% of the patients received intra-arterial contrast (of these 60% coronary catheterisations, 30% percutaneous coronary interventions and 10% other). Serum creatinine was measured immediately before, at 2-6 days, and at 26-35 days after contrast administration. PC-AKI was defined as an increase of serum creatinine >25% or >44 µmol/L 2-6 days after contrast (instead of the usual 48-72 hours after contrast). Outcomes of interest were incidence of contrast-induced nephropathy, renal failure, dialysis and renal function decline.

Nijssen (2018) presented the 1-year follow-up results of the study of Nijssen (2017). For inclusion criteria see above. Outcomes of interest were renal function decline and dialysis.

Timal (2020) performed a multicentre, noninferiority, randomized clinical trial (KOMPAS) in the Netherlands to determine the safety of omitting prophylactic prehydration prior to iodine-based contrast media administration in the setting of elective contrast-enhanced CT. Inclusion criteria were patients with an estimated glomerular filtration rate (eGFR) of 30 to 44 mL/min/1.73 m² (CKD stage 3B) or with an eGFR of 45 to 59 mL/min/1.73 m² (CKD stage 3A) in the presence of diabetes or at least 2 of the following risk factors: peripheral artery disease, congestive heart failure, age older than 75 years, anemia, contrast medium volume greater than 150 mL, or use of nephrotoxic medication (e.g., diuretics, nonsteroidal anti-inflammatory drugs, cyclosporin, tacrolimus, antiviral medication, amphotericin B, aminoglycosides, cisplatin, vancomycin). In total, 261 patients received prehydration with 250 mL of 1.4% sodium bicarbonate administered in a 1-hour infusion and 262 patients received no prehydration. Groups were comparable at baseline with amongst others 40% diabetes and approximately 15% heart failure in both groups. About half of the patients had an eGFR 30-45 ml/min/1.73m². Approximately 50% of the patients were using diuretics, which could be interrupted before contrast administration. Serum creatinine was measured before hydration and contrast, at 2-5 days, and at 7-14 days after contrast administration in all patients and was repeated after 2 months in the patients who had developed PC-AKI. PC-AKI was defined as an increase of serum creatinine >25% or >44 µmol/L 2-5 days after contrast. Outcomes of interest were incidence of postcontrast acute kidney injury (PC-AKI), irreversible loss of kidney function and dialysis.

Table 2. Characteristics of included studies

_{*For further details, see risk of bias table in the appendix}

_{** The risk of bias was based on the risk of bias assessment performed in the guideline of 2017}

Results

1. Post-contrast acute kidney injury (PC-AKI) (critical)

Four studies reported the incidence of PC-AKI for the comparison between hydration and no hydration (Chen, 2008; Kooiman, 2014; Nijssen, 2017; Timal, 2020). Because of heterogeneity between these studies in terms of type of hydration, the results were not pooled.

Chen (2008) reported that 22 of the 330 patients (6.67%) in the group with normal or mildly impaired renal function (eGFR 53±16 ml/min/1.73m²) who received hydration with 0.45% NaCl had PC-AKI as compared to 23 of the 330 (6.97%) who received no hydration (RR=0.89, 95%CI 0.58 to 1.35). In the group with moderate to severely impaired renal function (eGFR 28±2 ml/min/1.73m²), 40 of the 188 patients (21.28%) who received hydration had PC-AKI as compared to 64 of the 188 patients (34.04%) who received no hydration (RR=0.63, 95%CI 0.46 to 0.84).

Kooiman (2014) reported that 5 of the 70 patients (7.1%) who received 1-hour pre-hydration with 250ml NaHCO3 had PC-AKI as compared to 6 of the 65 patients (9.2%) in the group withholding hydration (RR=0.77, 95%CI 0.25 to 2.41).

Nijssen (2017) reported that 8 of the 296 patients (2.7%) who received hydration had contrast-induced nephropathy as compared to 8 of the 307 patients (2.6%) who did not receive hydration (RR=1.04, 95%CI 0.39 to 2.73).

Timal (2020) reported that 4 of the 261 patients (1.5%) who received hydration had PC-AKI 2 to 5 days after contrast enhanced CT as compared to 7 of the 262 patients (2.7%) who did not receive hydration (RR=0.57, 95%CI 0.17 to 1.94).

2. Start renal replacement therapy (RRT) (critical)

Three studies reported the start of renal replacement therapy for the comparison between hydration and no hydration (Nijssen, 2014; Nijssen, 2017; Timal, 2020). Because of heterogeneity between these studies in terms of type of hydration and since no events occurred, the results were not pooled.

Nijssen (2014) reported that none of the PC-AKI patients who either received hydration or no hydration developed need for dialysis.

Nijssen (2017) reported that no patients who received either hydration or did not receive hydration required dialysis within 35 days post-contrast.

Timal (2020) reported that during the at least one-year follow-up, no patients who received either hydration or did not receive hydration required dialysis.

At 1-year follow-up

Nijssen (2018), the 1-year follow-up study of Nijssen (2017), reported that within 365 days, 2 of the 328 patients (0.6%) who received hydration required dialysis as compared to 2 of the 332 patients (0.6%) who did not receive contrast (RR=1.01, 95%CI 0.14 to 7.14).

3. Acute renal failure (important)

Not reported.

4. Irreversible loss of kidney function (important)

Timal (2020) reported that after 2 months of follow-up, 3 of the 7 patients (43%) with PC-AKI who did not receive hydration had a persisting decline of renal function (mean decrease in eGFR, 3 mL/min/1.73 m²) while this did not occur in the 4 patients who developed PC-AKI despite hydration (RR=0.23, 95%CI 0.01 to 3.56).

4.1. >10 ml/min/1.73m² eGFR decline

Nijssen (2017) reported that 7 of the 260 patients (2.7%) who received hydration had >10 ml/min/1.73m² renal function decline from baseline as compared to 11 of the 260 patients (4.2%) who did not receive hydration (RR=0.64, 95%CI 0.25 to 1.62). This difference is clinically relevant favoring hydration.

1-year follow-up

Nijssen (2018), the 1-year follow-up study of Nijssen (2017), reported that 28 of the 297 patients (9.4%) who received hydration had >10 ml/min/1.73m² renal function decline from baseline as compared to 28 of the 292 patients (9.6%) who did not receive hydration (RR=0.98, 95%CI 0.60 to 1.62). This difference is not clinically relevant.

4.2. Decline to <30 mL per min/1.73m²

Nijssen (2017) reported that 7 of the 260 patients (2.7%) who received hydration had a renal function decline to eGFR < 30 mL per min/1.73m² as compared to 6 of the 260 patients (2.3%) who did not receive hydration (RR=1.17, 95%CI 0.40 to 3.42).

1-year follow-up

Nijssen (2018), the 1-year follow-up study of Nijssen (2017), reported that 9 of the 297 patients (3.0%) who received hydration had a renal function decline to eGFR
< 30 mL per min/1.73m² as compared to 8 of the 292 patients (2.7%) who did not receive hydration (RR=1.11, 95%CI 0.43 to 2.83).

5. Adverse events (important)

Nijssen (2017) reported that 13 of the 328 patients (4.0%) who received short or long hydration with NaCl 0.9% had symptomatic heart failure, while this did not occur in patients who did not receive hydration (RR=27.33, 95%CI 1.63 to 457.82).

Timal (2020) reported that no patients who received either hydration (n=261) or did not receive hydration (n=262) developed heart failure.

Q2: NaCl versus NaHCO3

Description of studies

A total of 27 studies were included in the analysis of the literature. Twenty-four RCTs were found and described in the search of 2017. This was updated in 2025 with the description of three additional studies. Important study characteristics and results are summarized in table 4. The assessment of the risk of bias is summarized in the risk of bias tables (under the tab ‘Evidence tabellen’).

Description of three studies from update 2025

Boccalandro (2020) performed a prospective, single-centre, randomized, double-blinded

study in the USA to compare the effect of a short schedule of sodium bicarbonate with NaCl on long-term outcomes of clinically stable patients with chronic kidney disease (CKD) undergoing non-emergent coronary angiography and when indicated percutaneous coronary intervention. It included elective cases and urgent cases defined as requiring angiography within 24-hours from hospital admission with CKD Stage III-IV (eGFR 15-59 ml/min/1.73 m²). In total, 190 patients received NaCl (154mEq/l NaCl with 5% dextrose solution for 1 h before and during the angiographic procedure at a rate of 3ml/kg/h followed by 1 ml kg/h for 6 h post-procedure ) and 192 patients received sodium bicarbonate (150 mEq/l SB with 5% dextrose solution at 3 ml/kg/h for 1 h before and during the angiographic procedure, followed by 1 ml/kg/h for 6 h post-procedure). Diuretics and non-steroidal anti-inflammatory drugs were discontinued 24-hours prior to the procedure and at least for 72-hours after the procedure. Groups were comparable at baseline. Gender was equally distributed with 53% and 51% male in the sodium bicarbonate group and sodium chloride group, respectively. Within the sodium bicarbonate group, 60% were of Caucasian descent, 30% of Hispanic descent and 10% of African American descent. These figures were comparable within the sodium chloride group, being 62%, 29% and 8%, respectively. Baseline eGFR was 40±18 ml/min/1.73m² and 63% had diabetes mellitus. Outcomes of interest were iodine containing contrast associated acute kidney injury (CA-AKI) defined by an absolute increase in creatinine >0.5 mg/dl (>44 µmol/l) or relative increase >25% within 48 hours and need to start renal replacement therapy after 1 and 5 years based on telephone interview of randomized patients.

Weisbord (2018) performed a double-blind, placebo- and comparator-controlled, multicentre, international randomized clinical trial with a 2 by 2 factorial design comparing intravenous sodium bicarbonate with intravenous sodium chloride and oral acetylcysteine with oral placebo for the prevention of major adverse outcomes and acute kidney injury in a large population of high-risk patients undergoing coronary or noncoronary angiography. Patients were enrolled at 53 medical centres in the United States of America (35 Veteran Affairs sites), 13 sites in Australia, 3 sites in Malaysia, and 2 sites in New Zealand. For the purpose of this guideline, only the comparison between sodium chloride and sodium bicarbonate were analysed. Patients (93.6% male; 80.9% with diabetes) undergoing non-emergency coronary or non-coronary angiography who had a baseline eGFR of 15 to 44.9 ml/min/1.73 m² or both an eGFR of 45 to 59.9 ml/min/1.73 m² and diabetes were included. In total, 2482 patients received isotonic 0.9% sodium chloride (154 mmol/l) and 2511 patients received isotonic 1.26% sodium bicarbonate (150 mmol/l). The infusion protocol allowed different volume and duration of infusion in the protocols of the participating centers with a specified minimum required volume and duration of administration of ≥3 ml/kg over 1-12 hours (1-3 ml/kg/hour) before angiographic procedure, 1–1.5 ml/kg/hour during angiography, and ≥6 ml/kg over 4-12 hours (1–1.5 ml/kg/hour) after the procedure. Blood samples were collected before, 3-5 days and 90-104 days after angiography and serum creatinine levels in these samples were measured simultaneously for each patient in the trial laboratory. Groups were comparable at baseline. The outcomes of interest were CA-AKI (increase of serum creatinine ≥25% and/or ≥0.5 mg/dl (44 µmol/l) at 96 hours) and need for dialysis or persistent decline in kidney function (increase of creatinine >50% from baseline) at 90 days. The trial was stopped prematurely because of futility after the preplanned interim analysis after inclusion of 4993 patients.

Garcia (2018) performed a subgroup analysis of the study of Weisbord (2018) to assess the effect of intravenous sodium bicarbonate and intravenous sodium chloride in patients who underwent percutaneous coronary intervention (PCI) during the angiographic examination. Patients were excluded in the case of emergency angiography (e.g., those with ST-segment elevation myocardial infarction); unstable baseline levels of serum creatinine (≥ 25% variation within 3 days prior to angiograph); decompensated heart failure requiring IV inotropic support, ultrafiltration, or intra-aortic balloon pump; recent exposure to contrast media. In total, 593 patients received sodium chloride, and 568 patients received sodium bicarbonate. Groups were comparable at baseline. Baseline median eGFR was 50.7 ml/min/1.73m² (IQR 41.7 – 60.1). Patients undergoing PCI received a median contrast volume of 160 ml (IQR 115 – 220) versus non-PCI median 75 ml (IQR 50 – 105) in the overall cohort of Weisbord 2018. The outcome of interest was CA-AKI.

Description of all current and previous studies

Depending on the design, the RCTs comparing sodium to bicarbonate hydration were categorized into several groups:

1. Short schedule NaHCO₃ vs. short schedule NaCl in patients with impaired kidney function undergoing coronary angiography (CAG) and/or PCI. A total of 11 RCTs (Adolph, 2008; Boccalandro, 2020; Boucek, 2013; Brar, 2008; Gomes, 2012; Masuda, 2007; Merten, 2004; Ozcan, 2007; Ratcliffe, 2009; Recio-Mayoral, 2007; Solomon 2015) with 2,192 patients were identified, that compared bicarbonate and sodium chloride hydration in a similar hydration scheme for coronary angiography. All the studies were performed in patients with impaired kidney function;
2. Short schedule NaHCO₃ vs. long schedule NaCl (1ml/kg/h for 12h pre- and 12h post-CM administration) in patients with impaired kidney function undergoing CAG and/or PCI. A total of 9 RCTs (Briguori, 2007; Castini, 2010; Hafiz, 2012; Klima, 2012; Koc, 2013; Lee, 2011; Maioli, 2008; Nieto-Rios, 2014; Shavit, 2009) with 3,026 patients were identified that compared bicarbonate hydration to sodium chloride pre- and posthydration (1ml/kg, 12hour pre- and post) for coronary angiography;
3. All other hydration schedules comparing bicarbonate plus sodium chloride or bicarbonate only to either sodium chloride or bicarbonate only. Four RCTs (Chong, 2015; Motohiro, 2011; Tamuro, 2009; Ueda, 2011) with 358 patients compared bicarbonate to sodium chloride hydration with divergent hydration schemes for coronary angiography, like adding a bolus NaHCO₃ to sodium chloride hydration or exchanging sodium chloride by NaHCO₃ hydration for multiple hours. One study (Weisbord, 2018) with 4,993 patients compared bicarbonate to sodium chloride hydration with an infusion protocol allowing different volume and duration of infusion in the protocols of the participating centers with a specified minimum required volume and duration of administration (see above) for coronary angiography and Garcia (2018) performed a subgroup analysis for 1,161 patients receiving PCI;
4. One RCT compared in a non-inferiority trial, a 1-hour schedule of 250ml NaHCO₃ 1.4% versus 1000 ml NaCl 0,9% in 4-12h pre- and 4-12h post-CM administration in 548 CT patients. (Kooiman, 2014).

Table 4. Characteristics of included studies

_{* For further details, see risk of bias table in the appendix}

_{** The risk of bias was based on the risk of bias assessment performed in the guideline of 2017}

Results

1. Post-contrast acute kidney injury (PC-AKI) (critical)

Depending on the design, the RCTs comparing sodium to bicarbonate hydration were categorized into several groups:

1. Short schedule NaHCO₃ (3ml/kg/h 1 hour pre and 1ml/kg/h 6 hours post CM administration) vs. short schedule NaCl in patients with impaired kidney function undergoing CAG and/or PCI. A total of 11 RCTs with 2,192 patients and 237 PC-AKI events were identified (Adolph, 2008; Boccalandro, 2020; Boucek, 2013; Brar, 2008; Gomes, 2012; Manari, 2014; Masuda, 2007; Ozcan, 2007; Ratcliffe, 2009; Recio-Mayoral, 2007; Solomon 2015). No significant difference was found between patients that underwent bicarbonate versus sodium chloride hydration: Risk Ratio (RR): 0.89 (95% CI: 0.57 – 1.39), p=0.63, I2=56%, as shown in Figure 1.
2. Short schedule NaHCO₃ (3ml/kg/h 1 hour pre and 1ml/kg/h 6 hours post CM administration) vs. long schedule NaCl (1ml/kg/h 12 hours before and after CM administration) in patients with impaired kidney function undergoing CAG and/or PCI. A total of 9 RCTs (Briguori, 2007; Castini, 2010; Hafiz, 2012; Klima, 2012; Koc 2013; Lee, 2011; Maioli, 2008; Nieto Rios, 2014; Shavit, 2009) with 2,994 patients and 272 PC-AKI events were identified that compared bicarbonate hydration to sodium chloride pre- and posthydration (1ml/kg, 12hour pre- and post) for coronary angiography. No significant difference was found between patients that underwent bicarbonate versus sodium chloride hydration: Risk Ratio (RR): 1.23 (95% CI: 0.81 – 1.87), p=0.33, I²=47% as shown in Figure 2.
3. All other hydration schedules comparing bicarbonate plus sodium chloride or bicarbonate only to either sodium chloride or bicarbonate only. A total of 6 RCTs (Chong, 2015; Garcia, 2018; Motohiro, 2011; Tamura, 2009; Ueda, 2011; Weisbord, 2018) with 5,661 patients and 503 PC-AKI cases, were considered suitable for this literature summary. The studies were considered too heterogenous in terms of hydration fluid content and hydration schemes in control group and treatment group to be considered for pooling. Chong, 2015 reported that PC-AKI incidences were 10/153 (6.5%) in the group receiving NaCl plus NAC, and 16/151 (10.6%) in the group bicarbonate plus NAC. The difference in PC-AKI incidence between groups was not significant. Motohiro, 2011 reported that 2/78 patients in the bicarbonate plus sodium chloride group versus 10/77 in the standard hydration group (RR: 0.20, 95% CI: 0.04 to 0.87) developed PC-AKI, thus the incidence of PC-AKI was lower in the combination group. Tamura, 2009 also reported lower rates of PC-AKI in the bolus group: 1/72 versus 9/72 (RR: 0,11; 95% CI: 0.01 to 0.85. The results of Ueda, 2011 were similar, although the difference in incidence of PC-AKI was not statistically significant: 2/30 versus 8/29 PC-AKI cases; RR: 0.24 (95% CI: 0.06 to 1.04). Weisbord (2018) reported that 206 of the 2482 patients (8.3%) who received NaCl had CA-AKI as compared to 239 of the 2511 patients (9.5%) who received NaHCO3 (RR=0.87, 95%CI 0.73 to 1.04). In addition, Garcia (2018) reported that 71 of the 593 patients (12.0%) who underwent coronary angiography with PCI and received NaCl had CA-AKI as compared to 64 of the 568 patients (11.3%) who received NaHCO3 (RR=1.06, 95%CI 0.77 to 1.46).
4. Kooiman, 2014 reported a PC-AKI incidence of 4.1% in CT patients receiving 250ml NaHCO₃ (ultrashort schedule) precontrast versus 5.1% (p=0.23) receiving pre- and post-CM hydration with NaCl 0,9%..

Figure 1. Pooled analysis of PC-AKI risk in patients receiving short schedules of hydration with either bicarbonate or sodium chloride for CAG/PCI

Figure 2. Pooled analysis of PC-AKI risk in patients receiving short schedules for bicarbonate versus long schedule for sodium chloride for CAG/PCI

2. Start renal replacement therapy (RRT) (critical)

Depending on the design, the RCTs comparing sodium to bicarbonate hydration were categorized into several groups:

1. Short schedule NaHCO₃ (3ml/kg/h 1 hour pre and 1ml/kg/h 6 hours post CM administration) vs. short schedule NaCl in patients with impaired kidney function undergoing CAG and/or PCI. A total of nine RCT’s (Adolph, 2008; Boccalandro, 2020; Boucek, 2013; Brar, 2008; Merten, 2004; Ozcan, 2007; Ratcliffe, 2009; Recio-Mayoral, 2007; Solomon, 2015) reported the requirement of dialysis.  
2. Short schedule NaHCO₃ (3ml/kg/h 1 hour pre and 1ml/kg/h 6 hours post CM administration) vs. long schedule NaCl (1ml/kg/h 12 hours before and after CM administration) in patients with impaired kidney function undergoing CAG and/or PCI. A total of seven studies (Briguori, 2007; Castini, 2010; Hafiz, 2012; Klima, 2011; Lee, 2011; Maioli, 2008; Nieto-Rios, 2014; Shavit, 2009) reported the requirement of dialysis.
3. All other hydration schedules comparing bicarbonate plus sodium chloride or bicarbonate only to either sodium chloride or bicarbonate only. A total of five studies (Chong, 2015; Motohiro, 2011; Tamuro, 2009; Ueda, 2011; Weisbord, 2018) reported the requirement of dialysis.
4. The requirement for dialysis in patients receiving ultrashort schedule bicarbonate versus pre- and post-CM hydration with NaCl was reported by the study of Kooiman 2014.

In table 5, the dialysis requirement is shown for all the sodium chloride versus sodium bicarbonate hydration comparisons. Because of the diversity of the included studies and the low number of events, these studies were not pooled. The studies found in the update of 2025 had a greater sample size and more events occurred and were described in more detail below.

Boccalandro (2020) reported that 6 of the 190 patients (3.2%) who received NaCl had procedure related renal replacement therapy as compared to 8 of the 192 patients (4.2%) who received NaHCO3 (RR=0.76, 95%CI 0.27 to 2.14).

Weisbord (2018) reported that 29 of the 2482 patients (1.2%) who received NaCl needed dialysis by 90 days as compared to 32 of the 2511 patients (1.3%) who received NaHCO3 (RR=0.92, 95% CI 0.56 to 1.51).

1-year RRT

Boccalandro (2020) reported that after 1 year, 1 of the 190 patients (0.5%) who received NaCl required permanent renal replacement therapy as compared to 4 of the 192 patients (2.1%) who received NaHCO3 (RR=0.25, 95%CI 0.03 to 2.24).

5-year RRT

Boccalandro (2020) reported that after 5-years, 22 of the 190 patients (11.6%) who received NaCl required renal replacement therapy as compared to 19 of the 192 patients (9.9%) who received NaHCO3 (RR=1.17, 95%CI 0.66 to 2.09).

3. Acute renal failure (important)

Not reported.

4. Irreversible loss of kidney function (important)

Weisbord (2018) reported that 28 of the 2511 patients (1.1%) who received NaCl had persistent kidney impairment by 90 days as compared to 25 of the 2482 patients (1.0%) who received NaHCO3 (RR=1.11, 95%CI 0.65 to 1.89).

5. Adverse events (important)

Depending on the design, the RCTs comparing sodium to bicarbonate hydration were categorized into several groups:

1. Short schedule NaHCO3 (3ml/kg/h 1 hour pre and 1ml/kg/h 6 hours post CM administration) vs. short schedule NaCl in patients with impaired kidney function undergoing CAG and/or PCI. A total of five studies (Boccalandro, 2020; Merten, 2004; Ozcan, 2007; Ratcliffe, 2009; Recio-Mayoral, 2007) reported the adverse event heart failure.
2. Short schedule NaHCO3 (3ml/kg/h 1 hour pre and 1ml/kg/h 6 hours post CM administration) vs. long schedule NaCl (1ml/kg/h 12 hours before and after CM administration) in patients with impaired kidney function undergoing CAG and/or PCI. A total of four studies (Hafiz, 2012; Klima, 2011; Lee, 2011; Nieto-Rios, 2014) reported the adverse event heart failure.
3. All other hydration schedules comparing bicarbonate plus sodium chloride or bicarbonate only to either sodium chloride or bicarbonate only. Four studies (Motohiro, 2011; Tamuro, 2009; Ueda, 2011; Weisbord, 2018) reported the adverse event heart failure.
4. Kooiman 2014 reported the adverse event heart failure in patients receiving ultrashort schedule bicarbonate versus pre- and post-CM hydration with NaCl.

In table 5, the adverse events (heart failure) are shown for all the sodium chloride versus sodium bicarbonate hydration comparisons. Because of the diversity of the included studies and the low number of events, these studies were not pooled. The studies found in the update of 2025 had a greater sample size and more events occurred and were described in more detail below.

Boccalandro (2020) reported that 26 of the 190 patients (13.7%) who received NaCl had heart failure as compared to 24 of the 192 patients (12.5%) who received NaHCO3 (RR=1.09, 95%CI 0.65 to 1.84).

Weisbord (2018) reported that 166 of the 2482 patients (6.7%) who received NaCl had heart failure as compared to 201 of the 2511 patients (8.0%) who received NaHCO3 (RR=0.84, 95%CI 0.69 to 1.02). In the study, on average 344 (274-445) ml of fluids were given before contrast, 114 (74-170) ml during contrast and 570 (471-669) ml after contrast, which is substantially less than in the original long schedule of 1ml/kg/h for 12h pre- and for 12h post contrast administration. Of note, only patients with decompensated heart failure requiring intensive therapy such as dobutamine or isolated ultrafiltration were excluded from this trial. Decisions on discontinuation of RAS blockers and diuretics were left to the treating physicians. There were no other relevant differences in adverse events between the two groups.

Table 5. Dialysis requirement and adverse events in bicarbonate versus sodium chloride infusion

_{NR: not reported}

Q3: Prehydration versus pre- and posthydration

Description of studies

A total of three studies were included in the analysis of the literature. One RCT was found in the search of 2017 and two studies were added in 2025. Important study characteristics and results are summarized in table 7. The assessment of the risk of bias is summarized in the risk of bias tables (under the tab ‘Evidence tabellen’).

Kooiman (2014) performed a randomized controlled, non-inferiority trial to compare a 1-hour schedule of 250ml NaHCO3 1.4% versus 1000 ml NaCl 0.9% in 4-12h pre- and 4-12h post-CM administration in 548 CT-patients.

Kooiman (2018) performed a multicenter randomized non-inferiority trial to determine whether pre-hydration with 1-hour sodium bicarbonate is non-inferior to pre- and post-hydration with sodium chloride in CKD patients undergoing elective cardiovascular diagnostic or other interventional contrast procedures requiring intra-arterial contrast administration. Patients 18 years or older with an eGFR <45 or an eGFR 45-60 ml/min in combination with diabetes mellitus or at least two other risk factors for the development of PC-AKI (i.e., peripheral arterial disease, congestive heart failure, age > 75 years, anemia, use of diuretics or non-steroidal anti-inflammatory drugs) were included. In total, 168 patients received 1-hour pre-procedural intravenous hydration with 250 ml 1.4% sodium bicarbonate and 165 patients received periprocedural intravenous hydration with 0.9% sodium chloride, 1000 ml in 4-12 hours prior to and 1000 ml in 4-12 hours following contrast administration (total volume 2000 ml). Groups were comparable at baseline except for an imbalance in type of contrast procedure. In the bicarbonate group 19.6% received contrast for CAG and 3% for PCI (18.2 and 1.8%, respectively in the sodium chloride group). Outcomes of interest were incidence of CI-AKI and need for dialysis.

Van Mourik (2018) performed an open-label single-center, unblinded, randomised non-inferiority trial to determine whether a short hydration protocol of 1 h sodium bicarbonate is non-inferior to conventional hydration with 24 h sodium chloride in consecutive patients with symptomatic aortic valve stenosis and impaired renal function who underwent pre-transcatheter aortic valve implantation (TAVI) computed tomography angiography (CTA). Patients with CKD classification 3a or above (eGFR <60ml/min/1.73m² based on the modification of diet in renal disease formula), age >18 years and planned for CTA prior to TAVI were included. 80% of the patients in the short hydration group were using diuretics and 63% in the conventional group and a small percentage was using other nephrotoxic drugs (5% and 11%, respectively). In the short hydration group in 91% of the patients the nephrotoxic medication was interrupted on the day of the CTA and in 75% in the conventional group. In total, 39 patients received 1h sodium bicarbonate prior to CTA (1.4% 3ml/kg/h) and 35 patients received 24h sodium chloride (0.9% 1ml/kg/h) 8h prior to CTA and 16h post-CTA. Groups were comparable at baseline. The outcome of interest was the occurrence of PC-AKI.

Table 7. Characteristics of included studies

_{* For further details, see risk of bias table in the appendix}

Results

1. Post-contrast acute kidney injury (PC-AKI) (critical)

Three studies reported the incidence of PC-AKI (Kooiman, 2014; Kooiman, 2018; Van Mourik, 2018) (figure 1). In total, 19 of the 466 patients (4.1%) who received prehydration with NaHCO3 had PC-AKI as compared to 26 of the 469 patients (5.5%) who received pre- and posthydration (RR=0.74, 95%CI 0.42 to 1.32). This difference is clinically relevant favoring prehydration.

Figure 1. Incidence of PC-AKI for comparison between prehydration and pre- and posthydration

2. Start renal replacement therapy (RRT) (critical)

Three studies reported the start of renal replacement therapy for the comparison between prehydration and pre- and posthydration (Kooiman, 2014; Kooiman, 2018; Van Mourik, 2018). Since no events occurred, the results were not pooled.

Kooiman (2014) reported that no patients who either received prehydration with NaHCO3 (n=264) or pre- and posthydration with NaCl (n=274) developed a need for dialysis.

Kooiman (2018) reported that no patient who either received prehydration with NaHCO3 (n=163) or pre- and posthydration with NaCl (n=160) required dialysis.

Van Mourik (2018) reported that none of the patients who either received prehydration with NaHCO3 (n=39) or pre- and posthydration with NaCl (n=35)

needed dialysis.

3. Acute renal failure (important)

Not reported.

4. Irreversible loss of kidney function (important)

Not reported.

5. Adverse events

Kooiman (2014) reported that acute heart failure due to volume expansion (based on the treating physician’s clinical judgement) occurred in none of the patients who received prehydration with NaHCO3 (n=267) versus 6 of the 281 patients (2.1%) who received pre- and posthydration with NaCl (RR=0.08, 95%CI 0.00 to 1.43).

Van Mourik (2018) reported that only 1 of the 35 patients (2.9%) who received pre- and posthydration with NaCl developed acute heart failure, while this did not occur in patients who received prehydration with NaHCO3 (n=39) (RR=0.30, 95%CI 0.01 to 7.13).

Question 4 and 5, not part of the update in 2024.

Q4 Oral versus intravenous hydration

Description of studies

One RCT (Cho, 2010) was considered suitable for inclusion in the literature summary. Cho, 2010 the RCT using both pre- and post-hydration consisted of 91 patients with sCr >97,2 µmol/l or eGFR <60 ml/min/1.73m² undergoing elective CAG. They were randomly assigned into 4 groups: A, NaCl 154mEq (0.9%)/l 3ml/kg/h 1 hour pre and 1ml/kg/h 6 hours post CM. B. NaHCO₃ 154mEq/l, same schedule as NaCl. C. 500ml of water, 4-2 hours pre-CM administration, followed by 600ml of water post contrast administration. D, C + 3.9g oral NaHCO₃ pre-CM and 1.95g oral NaHCO₃ post CM.

Results

Cho, 2010 also found no significant difference in the incidence of PC-AKI in all 4 groups: A 22.2%, B 9.5%, C 4.5% and D 4.8% (p>0.05).

Quality of evidence

For the comparison of oral versus intravenous hydration in all patients the level of evidence was graded as low due to imprecision and heterogeneity of included studies.

Q5 Hydration with controlled diuresis

Description of studies

Five Italian studies, all RCTs, describe the same technique, consisting of an extracorporeal circuit for continuous fluid infusion, combined with a Foley catheter for measuring urinary production (Barbanti, 2015; Briguori, 2011; Marenzi, 2012; Usmiani, 2016; Visconti, 2016) in respectively 112, 292, 170, 123, and 48 patients. This system is capable of delivering sterile replacement solution in an amount matched to the volume of urine produced, thereby avoiding hypovolemia and fluid overload. It displays urine and replacement volume and alerts to replace the fluid bag or drain the urine bag. After an initial bolus of 250ml NaCl 0.9% infused over 30 minutes, patients receive furosemide, 0.25mg/kg, to achieve a urinary flow of at least 300ml/h. Once this is achieved, the procedure is performed. The system keeps urinary flow >300ml/h for the next 4 hours, balancing between more NaCl and low dose furosemide.

Two of these three papers describe patients undergoing CAG and/or PCI (Marenzi, 2012; Usmiani, 2016), two papers describe patients undergoing Transcatheter Aortic Valve Implantation (TAVI) (Barbanti, 2015; Visconti, 2016) and one describes a mixed group of CAG and peripheral angiography (Briguori, 2011). All patients had eGFR <60 ml/min/1.73m², in one paper <30 ml/min/1.73m² (Briguori, 2011). The control group of each study had a different hydration schedule (sodium chloride versus bicarbonate versus a combination of both). Therefore, pooling of the studies was not possible due to heterogeneity.

Regarding the control group, Briguori, 2011 used 154 mEq/L of sodium bicarbonate in dextrose and water, mixed in the hospital pharmacy by adding 154mL of 1000 mEq/L sodium bicarbonate (i.e. sodium bicarbonate 8.4%) to 846 mL of 5% dextrose in water (D5W), slightly diluting the dextrose concentration to 4.23%. The initial intravenous bolus was 3 mL/kg per hour for at least 1 hour before contrast injection. Then, all patients received the same fluid at a rate of 1 mL/kg per hour during contrast exposure and for 6 hours after the procedure. All patients enrolled in this group received NAC orally at a dose of 1200 mg twice daily the day before and the day of administration of the contrast agent (for a total of 2 days). In this group, an additional NAC dose (1200 mg diluted in 100 mL sodium chloride) was administered intravenously during the procedure. The total NAC dose was 6g.

The control group of Marenzi, 2012 received a continuous intravenous infusion of isotonic sodium chloride at a rate of 1 ml/kg/h (0.5 ml/kg/h in case of left ventricular ejection fraction <40%) for at least 12 h before and 12 h after the procedure. The control group of Usmiani, 2016 received 1000 mL isotonic sodium chloride i.v. administration 12 h before procedure (rate-adjusted according to LVEF: 20– 40mL/h if LVEF<30%, 80–120 mL/h if LVEF 30–50%, 200 mL/h if LVEF >50%), plus 3 mL/kg/h sodium bicarbonate 1.4% solution by i.v. infusion for 1 h before procedure, plus 5000mg of Vitamin C and 1200mg NAC administered orally. After the procedure the patients received 1mL/kg/h sodium bicarbonate 1.4% solution IV for 6 hours, plus 5000mg of vitamin C and 1200mg NAC administered orally on the following day.

Barbanti, 2015 included 112 patients undergoing Transcatheter Aortic Valve Implantation (TAVI) who were randomly assigned to either the controlled diuresis group (n=56) or the control group (intravenous sodium chloride solution at a rate of 1 ml/kg/h 12 h before TAVI, during contrast exposure, and for 6 h after the procedure).

Viconti, 2016 describes also a group of patients undergoing TAVI (n=48) with either controlled diuresis or bicarbonate schedule (same schedule as Briguori, 2011). In total, 48 patients were assigned (non-randomly) to the RenalGuard therapy group (n=22) or the control group (n=26). Because the above-mentioned studies used different hydration schemes and methods, the studies could not be pooled.

Brar, 2014 described a slightly different approach: during CAG, a left ventricular catheter was placed in order to measure left ventricular end-diastolic pressure. This was done in 178 patients with eGFR <60 ml/min/1.73m² and one or more additional risk factors, such as diabetes, congestive heart failure, hypertension and age >75 years. The control group consisted of 172 patients with the same characteristics, undergoing the same procedure. Both groups received a bolus infusion, NaCl 0.9%, 3ml/kg/h, 1 hour pre-CAG. The control group received the same fluid at the same rate for 4 hours post CAG. The rate of post contrast fluid in the research group was dependent on the left ventricular end-diastolic pressure: <13mmHg 5ml/kg/h, 13 to 18mmHg 3ml/kg/h and >18mmHg 1.5ml/kg/h.

Another approach, described by Qian, 2016, is invasively measuring central venous pressure (CVP) and CVP-guided fluid administration in 264 patients. CVP <6mmHg 3ml/kg/h, CVP 6-12mmHg 1.5ml/kg/h, CVP>12mmHg 1ml/kg/h NaCl 0.9% 6 hours pre and 12 hours post CM administration. The control group received NaCl 1ml/kg/h 6 hours pre and 12 hours post CM administration. All patients were scheduled for CAG and/or PCI, had an eGFR 15-60 ml/min/1.73m² and LVEF <50% (Qian, 2016).

Results

Briguori, 2011, Marenzi, 2012 and Usmiani, 2015 all reported a significantly lower incidence of PC-AKI in patients who received controlled diuresis. Briguori, 2011 found an incidence of PC-AKI of 11% in the forced diuresis group versus 20.5% in the control group (p=0.025) in patients with an eGFR <30mL/min/1.73m². After 1 month, mortality was similar in the intervention (6/146) and control (6/146) group, p=0.99; need for dialysis arose in 7/146 patients in the control group versus 1/146 in the intervention group, p=0.03.

Marenzi, 2012 found an incidence of PC-AKI of 4,6% in the forced diuresis group versus 18% in the control group (p=0.005). In-hospital mortality was similar in the intervention (1/87) and control (2/82) group, p=0.53. Need for dialysis arose in 1/87 patients in the intervention group versus 3/83 in the control group, p=0.29.

Usmiani, 2016 found an incidence of PC-AKI of 7% in the forced diuresis group versus 25% in the control group (p=0.01). One-year mortality was not significantly different in the intervention (4/59) and control (8/65) group, p=0.46. Need for dialysis arose in 0/59 patients in the intervention group versus 2/65 in the control group, (p-value not reported).

Barbanti reported that the incidence of CI-AKI was lower in the controlled diuresis group compared to the control group (intravenous), controlled diuresis: 4/56 (5.4%) vs control: 13/56 (13.3%) (p=0.014).

Visconti, 2016 reported that PC-AKI occurred in 10/26 (38.5%) patients in the control group and in 1/22 (4.5%) patients in the RenalGuard group (p=0.005, odds ratio [OR] 0.076, 95% confidence interval [CI]: 0.009-0.66).

Brar, 2014 described that PC-AKI occurred in 16.3% of the patients in the control group vs. 6.7% in the research group (p=0.005). After 6 months, mortality was lower in the intervention (1/196) compared to the control (8/200) group, p=0.037. Need for dialysis arose in 1/196 patients in the intervention group versus 4/200 in the control group, p=0.37.

Qian, 2016 reported that PC-AKI occurred in 15.9% in the CVP group vs. 29.5% in the standard hydration group (p=0.006). Need for dialysis arose in 4/134 patients in the intervention group versus 13/135 in the control group, p=0.019. Acute pulmonary edema occurred in 5/134 patients in the intervention group versus 4/135 in the control group, p=0.50. Mortality rates were not reported.

Quality of evidence

For the comparison of controlled diuresis versus IV hydration in all patients the level of evidence was graded as low due to imprecision and heterogeneity of included studies.

An updated systematic review of the literature was performed to answer the following question(s):

Which hydration strategy has to be used for patients that receive intravascular iodine containing contrast media and have a high risk of PC-AKI?

Table 1. PICO

_{* In 2024 an updated literature search was performed for question 1-3 but not for question 4 and 5 (search performed in June 2015). Therefore the search and select and summary of literature sections distinguishes question 4 and 5 from 1-3}

Relevant outcome measures

The guideline panel considered Post-Contrast AKI (PC-AKI), end stage renal failure and start of renal replacement therapy as a critical outcome measures for decision making; and acute renal failure, irreversible loss of kidney function and adverse events (especially heart failure related to hydration procedure) as important long-term outcome measures.

The guideline defined PC-AKI as described in the chapter 2.1 PC-AKI: Definities, terminologie en klinisch verloop in the Dutch guideline “Veilig gebruik van contrastmiddelen (NVvR, 2017)”.

A priori, the guideline panel did not define the other outcome measures listed above but used the definitions used in the studies.

The guideline panel defined the following as a minimal clinically (patient) important difference:

• Post-contrast acute kidney injury (PC-AKI): relative risk <0.91 or >1.10.
• Complications of PC-AKI (start renal replacement therapy, acute renal failure, irreversible loss in kidney function, adverse events): relative risk <0.91 or >1.10.

A difference of at least 10% in relative risk was defined as a minimal clinically (patient) important difference; by expert opinion of the working group (no literature was available to substantiate the decision). To illustrate, if PC-AKI occurs with an incidence of 10% in the patient population, a difference of 10% of relative risk would mean a difference of 1% in absolute risk. Thus, the number needed to treat would be 100, ergo: a doctor would need to treat 100 patients to prevent one case of PC-AKI. When the incidence of PC-AKI is 5%, a difference of 10% in relative risk would mean a difference of 0.5% in absolute risk, and a number needed to treat of 200.

Search and select (Methods)

For question 1-3 a follow-up systematic literature search was performed by a medical information specialist using the following bibliographic databases: Embase.com and Ovid/Medline. Both databases were searched from 2017 to 21 October 2024 for systematic reviews, RCTs and observational studies. Systematic searches were completed using a combination of controlled vocabulary/subject headings (e.g., Emtree-terms, MeSH) wherever they were available and natural language keywords. The overall search strategy was derived from three primary search concepts: (1) impaired renal function; (2) iodine-containing contrast media; (3) hydration. Duplicates were removed using EndNote software. After deduplication a total of 571 records were imported for title/abstract screening. Initially, 85 studies were selected based on title and abstract screening. After reading 35 studies in full text, 27 studies were excluded (see the exclusion table under the tab ‘Evidence tabellen’), and 8 studies were included.

For question 4 and 5: The databases Medline (OVID), Embase and the Cochrane Library were searched from January 2000 to 17th of June 2015 using relevant search terms for systematic reviews (SRs), randomized controlled trials (RCTs) and observational studies (OBS). The literature search procured 858 hits: 183 SRs, 572 RCTs and 103 OBS. An update of the search on April 14^th 2017 retrieved an additional 138 studies. Based on title and abstract a total of 47 studies were initially selected, and a total of 17 studies based on the updated search (64 in total). After examination of full text, a total of 19 + 10 (29 in total) studies were excluded and 28 + 7 studies definitely included in the literature summary. Of these one RCT (Cho, 2010) was considered suitable for inclusion in the literature summary for question 4 about Oral versus intravenous hydration. For question 5 about hydration with controlled diuresis, seven studies were included: Barbanti, 2015; Briguori, 2011; Marenzi, 2012; Usmiani, 2016; Visconti, 2016, Brar, 2014 and Qian, 2016.The search and select and literature analysis of 2017 can be found in the appendix.