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Abstract

Introduction

Postoperative acute kidney injury (AKI) is a common postoperative complication in cardiac surgery, with varying reported incidences and prognostic factors. Renal hypoperfusion is believed to be a key factor contributing to postoperative AKI. Near-infrared spectroscopy (NIRS) monitoring, which assesses regional tissue saturation (RSO₂), has been suggested as a tool to predict postoperative AKI. The aim of this systematic review was to examine the prognostic value of perioperative NIRS monitoring in predicting postoperative AKI in pediatric patients.

Methods and Results

After a systematic search in PubMed, EMBASE, and Cochrane library, twenty studies (1517 patients) were included. The inter-rater agreement on study quality was strong, yet a high risk of bias was identified.

Conclusion

The heterogeneity of the results—in part attributable to several potential confounding factors regarding study population, monitoring technique and the definition of AKI—together with the lack of a clear and consistent association between RSO₂ values and AKI, currently preclude recommending NIRS monitoring as a reliable and valid clinical tool to “predict” AKI in the individual patient.

Keywords

NIRS AKI cardiac anesthesia pediatric intensive care cardiac surgery cerebral oximetry children congenital heart disease near-infrared spectroscopy near infrared spectroscopy

Introduction

Postoperative acute kidney injury (AKI) is a common occurrence in pediatric cardiac surgery, with reported incidences ranging from 3.4%¹ to 86%.² Although various classification systems have been used in the diagnosis of AKI, the Kidney Disease Improving Global Outcomes (KDIGO) classification is now regarded as the standard diagnostic classification tool.³ Biomarkers such as Kidney Injury Molecule-1 (KIM-1) and Neutrophil Gelatinase-Associated Lipocalin (NGAL) have shown a higher sensitivity to detect more subtle forms of renal injury,⁴ but are still mostly used in research settings.⁵

Occurrence of postoperative AKI is dependent on several pre-existing factors, such as young age, chronic kidney disease, anemia, cardiopulmonary bypass duration, multiple cross clamps, and preoperative inotropic support.^6-8 Perioperative renal hypoperfusion and hypoxia due to intraoperative hypotension^9,10 have been associated with postoperative AKI.¹¹ It has been shown that children developing AKI are more likely to have prolonged mechanical ventilation,^12,13 longer intensive care unit stay,¹⁴ and can evolve to chronic kidney disease. The relevance of AKI as a postoperative complication goes beyond (acute or chronic) kidney injury itself, since AKI has also been linked to an increase in morbidity and mortality, with mortality rates up to 89%.^15,16

The use of near-infrared spectroscopy (NIRS) monitoring, which measures regional tissue saturation (RSO₂),¹⁷ enables the real-time detection of local tissue hypoxia. Some authors suggest that renal region tissue oxygenation (RrSO₂) can be directly monitored by placing NIRS sensors on the flank skin overlying the kidney.¹⁸

Additionally, assessment of cerebral (RcSO₂) or somatic (RsSO₂) tissue oxygenation can be a surrogate for evaluation of global systemic oxygenation and is considered a useful tool in predicting postoperative AKI.^19-22

Over the last decade, various studies tested the hypothesis that low intraoperative RrSO₂ values were associated with postoperative AKI, reporting variable findings—and in some centers, RrSO₂ measurements are routinely performed in cardiac surgery.^19,20,23,24 The aim of this systematic review was to investigate the prognostic value of perioperative RSO₂ values to predict postoperative AKI in pediatric patients undergoing cardiac surgery.

Methods

This systematic review was registered publicly in the International Prospective Register of Systematic Reviews (PROSPERO; registration number: CRD42021241770) and is reported according to the 2020 guidelines from the Preferred Reporting Items for Systematic Reviews and Meta-Analyses (PRISMA) statement.²⁵ In this review we choose to focus on the pediatric cardiac surgery population.

Search Strategy and Article Selection

Three databases were selected for the systematic search (PubMed, EMBASE, and Cochrane Library; supplemental file 1). The database search was conducted on the 18^th of February 2021 and repeated on the 18^th of February 2024. Since most clinically used AKI definitions have been formulated after 2006,^7,26 we have included studies from years 2006–2024.^27-29 We also reviewed the bibliographies of the final selected studies, to identify any other potentially relevant study that was not found through the systematic search.

Studies were considered eligible for inclusion if the following a priori established criteria were met:

1. Original clinical studies, performed in the perioperative period in pediatric patients undergoing cardiac surgery (below 18 years of age).

2. Studies investigating either renal region (RrSO₂), cerebral (RcSO₂), or somatic (RsSO₂) NIRS monitoring in the perioperative phase, defined as the day before surgery (preoperative), during surgery (intraoperative) and the days after surgery (post-operative).

3. Studies investigating the association of any of the RSO₂ values with postoperative AKI as a primary outcome.

4. Studies using any of the following AKI definitions:

- KDIGO criteria³ or modified KDIGO criteria (based only on serum creatinine, sCr)^30,31

- pRIFLE (pediatric Risk, Injury, Failure, Loss, End stage renal disease) criteria³²

- AKIN (Acute Kidney Injury Network) criteria³³

- (fractional) sCr increase²⁹

- Urine output and/or urinary and serum biomarkers as markers for renal dysfunction (e.g., KIM-1, NGAL, cystatin C, blood urea nitrogen and tissue inhibitor of metalloproteinases-2* insulin-like growth factor-binding protein 7 ([TIMP-2]*[IGFBP7]))³⁴

- estimated glomerular filtration rate

We excluded studies written in a language other than English, animal studies, case reports, review articles and conference abstracts. The search and bibliographic review were performed independently by two researchers (CKN and DM) using the web application Rayyan.³⁵

Definitions of RSO₂ Values

RSO₂ values are measured as percentage of tissue hemoglobin oxygen saturation and were presented as absolute values (%; with either mean ± standard deviation or median [interquartile range]), as decrease from baseline value (%), or as predefined calculations. The following RSO₂ values were presented in the included studies:

• RrSO₂

◦ Absolute RrSO₂ values (%),^1,30,36-44 or nadir of absolute RrSO₂ value (%).⁴⁵

◦ Predefined threshold RrSO₂ values (%) regarding total time (≥2 hours or <2 hours)¹² of RrSO₂ below 50%,² or ≥20% reduction from baseline⁴⁰ for at least 60 consecutive seconds,³¹ or 20 minutes.¹⁴

◦ RrSO₂25 score and RrSO₂65 score (%min): difference between the baseline RrSO₂ and the actual RrSO₂ value (if decreased ≥25% from baseline or if <65%, respectively), multiplied by the time (minutes) during which RrSO₂ is decreased ≥25% from baseline or is <65%, respectively.¹³

◦ RrSO₂ (%), calculated as a percentage of baseline pulse oximetry saturation (SpO₂).⁴⁶

• RcSO₂

◦ Absolute RcSO₂ values,^30,42-44,47 average RcSO₂ values (%) at specific time points.^48-50

◦ Predefined threshold RcSO₂ values (%).⁵¹

◦ RcSO₂ variability, calculated as the root mean square of successive differences (RMSSD).²³

• RsSO₂

◦ Absolute RsSO₂ values,⁴² or average RsSO₂ value (%) at specific time points.⁵⁰

Data Extraction and Analysis

The primary outcome variables were the RSO₂ values and their association with postoperative AKI. The following data were extracted from each study independently: 1. Publication-related data (first author, year, and journal), 2. Number of patients included, 3. Surgery type, 4. NIRS device type and location of sensor(s) placement, 5. RSO₂ values, 6. AKI diagnostic criteria, 7. AKI incidence (percentage), and 8. Relation of the RSO₂ values with postoperative AKI.

Data extracted from the studies were tabulated using Microsoft Excel 2010 (Redmond, USA). No meta-analysis was performed, due to the heterogeneity of the included studies. The risk of bias for each article was evaluated independently, using the “Quality Assessment Tool for Observational Cohort and Cross-Sectional Studies” of the National Heart, Lung, and Blood Institute,⁵² after which a consensus on the risk of bias was reached. We used R version 4 (R Core Team, Vienna, Austria, 2020) to determine the inter-rater agreement (Table 1).

Table 1.

Risk of Bias Check and Overall Rating of the Included Articles as Determined After Reaching Agreement Between the Researchers.

^¥Retrospective studies; Green = yes, red = no, yellow = not applicable/not reported/cannot determine. Summary of checklist items (the complete assessment tool is available at the following link: https://www.nhlbi.nih.gov/health-topics/study-quality-assessment-tools)⁵²: 1. Research question and objective, 2-4. Definition of study population, participation rate, inclusion and exclusion criteria, 5. Sample size definition, 6-8. Relationship between exposure(s) and outcome(s), 9-11. Definition and assessment of exposure(s) and outcome(s), 12. Blinding, 13. Loss to follow-up, 14. Statistical adjustment for confounding variables.

Results

The database search retrieved 5304 studies, of which 1221 were duplicates and were removed. We excluded 4049 studies after reviewing title and abstract, and 49 studies were eligible for full text reviewing. Twenty-nine studies were excluded after full text reviewing and 20 studies were included, comprising 1517 patients with a median [interquartile range] of 57 [47–95] patients per study (Figure 1).

Figure 1.

Flowchart with the inclusion and exclusion of articles in this systematic review.

The inter-rater agreement regarding the quality of the studies was “strong”⁵³ (percent agreement 86.8%, Cohen’s Kappa = 0.72, 95% CI 0.64–0.80, P < .001; Table 1).

A high risk of bias was identified in four main categories: sample size justification, assessment of different levels of exposure, blinding, and statistical adjustment for potential confounding variables.

Most studies included pediatric patients under 12 months of age. Four studies were performed in pediatric patients with non-cyanotic heart disease undergoing aortic arch reconstruction.^41,42,47,51 Fourteen studies had a mixed population, including both cyanotic and non-cyanotic pediatric patients, undergoing either corrective or palliative procedures.^{1,2,12-14,23,30,36,39,40,44-46,50} The reported incidence of postoperative AKI varied from 3.4%¹ and 86%.² The diagnostic AKI criteria used were the pRIFLE criteria (n = 7),^{12-14,39,43,47,50} the KDIGO criteria (n = 7),^{2,23,40-42,44,45} a modified KDIGO (using only sCr increase (n = 2),^30,31 initiation of renal replacement therapy (n = 2),^1,36 (fractional) sCr increase (n = 2),^12,46 and urine output (n = 1).⁵¹

Renal Region NIRS (RrSO₂)

Ten out of seventeen studies investigating RrSO₂ (Table 2) reported that RrSO₂ values were associated with postoperative AKI.^{12,13,30,31,36,39,40,44-46} The majority of them included both cyanotic and non-cyanotic pediatric patients.

Table 2.

Overview of the Included Studies.

First Author	Year	Number of Patients	Age	Device	Site of NIRS Monitoring	Period of Monitoring	AKI Definition	AKI Incidence	Comparison Variable	Strength of the Association NIRS-AKI	Other Findings

Miyamoto⁵¹ ^a ^b	2008	12	0–2 months	nr	Cerebral	Intraoperative	Urine output	nr	RcSO₂	No association	Higher RcSO₂ was associated with higher urine output during CPB
Owens¹²	2011	40	0–12 months	INVOS	Renal	Postoperative (48 h)	pRIFLE or sCr increase	25%	RrSO₂ (<50% for >2 h)	Subjects with RrSO₂ <50% for >2 h had higher AKI incidence (63% vs 16%, P = .015)
Owens¹²	2011	40	0–12 months	INVOS	Cerebral	Postoperative (48 h)	pRIFLE or sCr increase	25%	RcSO₂
Colasacco⁴⁶ ^c	2011	48	0–6 months	nr	Renal	Intraoperative and postoperative (48 h)	Fractional sCr increase	23%	RrSO₂ (% of baseline SpO₂)	Correlation RrSO₂ on POD1 – 40% fractional sCr increase: R² = 0.60
Colasacco⁴⁶ ^c	2011	48	0–6 months	nr	Renal	Intraoperative and postoperative (48 h)	Fractional sCr increase	23%	RrSO₂ (% of baseline SpO₂)	RrSO₂ <80% (Sn 100%, Sp 75%) or <75% (Sn 82%, Sp 97%) on POD1
Jung Kim⁴⁷ ^a ^b	2013	47	0–12 months	INVOS	Renal	Intraoperative	pRIFLE	40.4%	RrSO₂	No association
Jung Kim⁴⁷ ^a ^b	2013	47	0–12 months	INVOS	Cerebral	Intraoperative	pRIFLE	40.4%	RcSO₂	No association
Hazle²	2013	49	0–6 months	INVOS	Renal	Postoperative (24 h)	KDIGO	86%	RrSO₂ (<50%)	No association	Low RrSO₂ was associated with elevated urinary NGAL, IL-18, cystatin C and a poor outcome
Ruf¹³ ^c	2015	59	0–12 months	INVOS	Renal	Intraoperative and postoperative (24 h)	pRIFLE	48%	RrSO₂25 score	RrSO₂25 score >23 min%: Sn 67%, Sp 76%, AUROC 0.69	RrSO₂ performed better than cystatin C and NGAL in predicting AKI
Ruf¹³ ^c	2015	59	0–12 months	INVOS	Renal	Intraoperative and postoperative (24 h)	pRIFLE	48%	RrSO₂65 score	RrSO₂65 score <95 min%: Sn 96%, Sp 40%, AUROC 0.62
Gist¹⁴	2016	106	0–4 years	INVOS	Renal	Intraoperative and postoperative (24 h after CPB)	pRIFLE	32%	RrSO₂ (decrease ≥20% for 20 min)	No association	Low RrSO₂ was associated with longer mechanical ventilation and LOS
Neunhoeffer³⁹	2016	50	0–12 months	O2C	Renal	Postoperative (at 24 h)	pRIFLE	40%	RrSO₂	RrSO₂ <65%: Sn 80%, Sp 65.3%, AUROC 0.75 (repair of CHD)
Neunhoeffer³⁹	2016	50	0–12 months	O2C	Renal	Postoperative (at 24 h)	pRIFLE	40%	RrSO₂	RrSO₂ <61%: Sn 77.8%, Sp 62.5%, AUROC 0.73 (palliation of CHD)
Joffe⁴⁰ ^c	2018	66	Median (IQR): 5.9 (4.6–11.5) months	INVOS	Renal	Intraoperative	KDIGO	65%	RrSO₂	Baseline RrSO₂ in the highest tertile: AKI 7.14 times more likely compared to lowest tertile
Joffe⁴⁰ ^c	2018	66	Median (IQR): 5.9 (4.6–11.5) months	INVOS	Renal	Intraoperative	KDIGO	65%	RrSO₂	Higher average RrSO₂ during CPB is associated with increased AKI (OR 1.06)
Flechet²³ ^c	2019	156	0–12 years	Foresight	Cerebral	Postoperative	KDIGO	35%	RcSO₂ (mean; RMSSD)	Low RcSO₂ RMSSD associated with higher AKI risk (AUROC 0.68)	A clinical model had better predictive performance than RcSO₂
Adams⁴⁵ ^c	2019	70	0–12 months	INVOS	Renal	Intraoperative and postoperative (48 h)	KDIGO	61%	RrSO₂ (average and lowest value)	Stage 2-3 AKI patients had lower mean RrSO₂ (66% vs 79% for stage 1 AKI and 84% for no AKI, P = .038)	Low RrSO₂ was associated with elevated NGAL
Kulyabin⁴¹ ^a ^c	2020	45	0–1 month	nr	Renal	Intraoperative and postoperative (24 h)	KDIGO	42%	RrSO₂	No association
Kulyabin⁴¹ ^a ^c	2020	45	0–1 month	nr	Cerebral	Intraoperative and postoperative (24 h)	KDIGO	42%	RrSO₂	No association
Abbasciano³⁰ ^c	2021	34	0–6 months	EQUANOX	Renal	Intraoperative and postoperative (min. 24 h)	Modified KDIGO	20%	RcSO₂	Lower RrSO₂ values 6 h after surgery were associated with AKI (P = .043)
Abbasciano³⁰ ^c	2021	34	0–6 months	EQUANOX	Cerebral	Intraoperative and postoperative (min. 24 h)	Modified KDIGO	20%	RrSO₂
Zhang³¹ ^c ^d	2021	242	1–12 months	Foresight	Renal	Intraoperative	Modified KDIGO	31%	RrSO₂	RrSO₂ desaturation ≥20% for ≥60 sec is associated with AKI (OR 2.79 (1.21–6.44) P = .016)
Inoue⁵⁰ ^c ^d	2022	87	0–7 months	INVOS	Cerebral	Intraoperative	pRIFLE	23%	RcSO₂	RsSO₂ ≤74% is associated with AKI (AUC 0.82, P < .001)
					Abdomen				RsSO₂
					Thigh				RsSO₂
Shikata⁴² ^a ^b ^c	2022	28	0–3 months	INVOS	Cerebral	Intraoperative	KDIGO	39.3%	RcSO₂	RsSO₂ ≤48% for >20 min is associated with KDIGO stage >1 (ROC 0.78, Sn 0.7, Sp 0.78)
					Renal (flank)				RrSO₂
					Thigh				RsSO₂
Doctor⁴³ ^a ^b	2022	91	0–6 months	INVOS	Cerebral	Postoperative	pRIFLE	33%	RcSO₂	No association
Doctor⁴³ ^a ^b	2022	91	0–6 months	INVOS	Renal	Postoperative	pRIFLE	33%	RrSO₂	No association
Wakamatsu⁴⁴	2023	114	0–17 years	INVOS	Cerebral	Intraoperative	KDIGO	35.1%	RcSO₂	Lower baseline RcSO₂ were lower in AKI group (61 vs 69.5%; P = .031)
Wakamatsu⁴⁴	2023	114	0–17 years	INVOS	Renal	Intraoperative	KDIGO	35.1%	RrSO₂	Lower RcSO₂ and RrSO₂ during CPB in AKI group (61 vs 73%; P = .013 and 60 vs 77%; P = .001). Lower RcSO₂ and RrSO₂ nadir in AKI group (48.5 vs 54%; P = .039 and 53 vs 71%; P = .005). Higher intraoperative RrSO₂ decrease in AKI group (27.5 vs 13.4%; P = .012)
Kumar³⁶	2023	55	0–18 years	INVOS	Cerebral	Intraoperative and postoperative (48 h)	AKI requiring RRT	7.3%	RrSO₂	Lower RrSO₂ in AKI patients
Kumar³⁶	2023	55	0–18 years	INVOS	Renal	Intraoperative and postoperative (48 h)	AKI requiring RRT	7.3%	RrSO₂	Lower RrSO₂ in AKI patients
Kumar¹	2024	118	0–14 years	INVOS	Renal	Intraoperative and postoperative (24 h)	AKI requiring RRT	3.4%	RrSO₂	No association	No association with NGAL

Abbreviations: pRIFLE, pediatric risk, injury, failure, loss, end stage renal disease; KDIGO, kidney disease: improving global outcomes; modified KDIGO = only use of serum creatinine of the kidney disease: improving global outcomes; sCr, serum creatinine; RrSO₂, renal tissue oxygenation; RcSO₂, cerebral tissue oxygenation; RsSO₂, somatic tissue oxygenation (e.g., muscle); SpO₂, pulse oximetry saturation, LOS, length of stay; NGAL, neutrophil gelatinase-associated lipocalin; CPB, cardiopulmonary bypass; POD1, postoperative day 1; CHD, congenital heart disease; nr, not reported; RRT, renal replacement therapy.

R², coefficient of determination; OR, odds ratio; Sn, sensitivity; Sp, specificity; AUROC, area under the ROC curve; RMSSD, root mean square of successive differences; INVOS (Medtronic, Minneapolis, MN, USA); Foresight (Edwards Lifesciences Corp. Irvine, CA, USA); O2C (LEA Medizintechnik, Giessen, Germany).

^aStudies including only cyanotic patients.

^bRetrospective studies.

^cRelationship between NIRS variables and AKI were risk adjusted.

^dStudies including only non-cyanotic patients.

The RrSO₂ was lower in preoperatively cyanotic patients at baseline^12,40 but not during cardiopulmonary bypass (CPB)^13,40 and after surgery.¹³ RrSO₂ values associated with a higher incidence of postoperative AKI were a low perioperative mean RrSO₂^36,44 (66% vs 84% in patients without AKI),⁴⁵ intraoperative RrSO₂ desaturation ≥20% for ≥60 seconds,³¹ an intraoperative RrSO₂25 score >23 min%¹³ or an intraoperative RrSO₂65 score <95 min%,¹³ lower RrSO₂ values at 6 hours postoperatively,³⁰ a postoperative RrSO₂ <50% for >2 hours,¹² a postoperative mean RrSO₂ <80% (higher sensitivity) or <75% (higher specificity) of individual baseline SpO₂,⁴⁶ and a postoperative RrSO₂ <65% or <61% (corrective or palliative surgical procedures, respectively).³⁹ The lowest intraoperative RrSO₂ value predicted postoperative increases in urinary NGAL and [TIMP-2]*[IGFBP7],⁴⁵ and patients spending more cumulative time with postoperative RrSO₂ values <50% had increased postoperative levels of urinary biomarkers (NGAL, IL-18 and cystatin C).² In one study higher RrSO₂ values before or during CPB were associated with the development of postoperative AKI.⁴⁰ The remaining seven studies (of which four including solely cyanotic patients^41-43,47) did not find an association between RrSO₂ and postoperative AKI.^{1,13,14,41-43,47}

Cerebral NIRS (RcSO₂)

Pediatric patients who developed AKI had a lower maximum RcSO₂ value (76% vs 79%) and a lower RMSSD (variability of RcSO₂ that takes gradual shifts in mean into account) as reported by one study.²³ Another study reported lower RcSO₂ values before surgery (61% vs 69.5%) and during CPB (61% vs 73%) in patients developing AKI.⁴⁴ The other eight studies found no association between RcSO₂ values and postoperative AKI in cyanotic patients,^42,43,47,51 in a mixed cyanotic and non-cyanotic population,^12,30 and in non-cyanotic patients.^31,50

Somatic NIRS (RsSO₂)

RsSO₂ values ≤74% measured at the thigh muscle in non-cyanotic patients undergoing ventricular septum defect repair were associated with postoperative AKI.⁵⁰ In aortic arch reconstruction with high-flow regional cerebral perfusion, a RsSO₂ ≤48% for >20 min was associated with development of postoperative AKI (KDIGO stage >1).⁴²

Discussion

The aim of this systematic review was to investigate the prognostic value of perioperative RSO₂ values to predict postoperative AKI in pediatric patients undergoing cardiac surgery. The findings of this review preclude the use of NIRS monitoring as a valid clinical tool to predict postoperative AKI.

Key Findings

Low RrSO₂ values were associated with postoperative AKI in nine out of seventeen studies. One of these seventeen studies reported an association between higher intraoperative RrSO₂ values and postoperative AKI. Only two out of nine studies reported an association of postoperative AKI with low RcSO₂ values in pediatric cardiac surgery. Postoperative AKI was associated with lower RsSO₂ in both studies reporting this measurement. Threshold RSO₂ values under which postoperative AKI was likely to develop were extremely variable, making it difficult to establish threshold values for clinical practice. Therefore, the current evidence precludes recommending the use of NIRS monitoring as a valid clinical tool to predict AKI in the individual patient.

Study Population, Monitoring Site, and AKI Definition

A challenge to drawing comprehensive conclusions stemmed from the inclusion of patients with both cyanotic and non-cyanotic heart disease, which represent distinct pathophysiological profiles with varying baseline RrSO₂ values.⁴⁰ In studies involving a mixed patient population, low RrSO₂ and/or RcSO₂ values were associated with AKI in eight and two out of 13 studies, respectively. None of the studies involving cyanotic pediatric patients found an association between RrSO₂, RcSO₂, and the development of postoperative AKI. In cyanotic pediatric patients,⁴⁰ low preoperative arterial oxygen saturation could play a protective role against perioperative kidney dysfunction, by a chronic reduction of metabolic rate of the brain and kidneys (“ischemic preconditioning”)⁵⁴ keeping RrSO₂ and RcSO₂ values close to their preoperative baseline values.

RcSO₂ values have been suggested to be a surrogate of tissue oxygenation in general⁵⁵ and could be an indirect RrSO₂ monitor.^24,56 The prognostic value of RcSO₂ to predict AKI in the pediatric population seems lower compared with RrSO₂ values or RsSO₂ values. A possible explanation is that the kidneys and other tissues (like muscles) suffer from hypoperfusion before the brain, due to hierarchical distribution of blood flow⁵⁷ and differences in organ blood flow autoregulation.⁵⁸

Proper placement of NIRS sensors for measuring RrSO₂ may contribute to the variability of the results. Only three studies reported the use of ultrasound imaging when placing the NIRS sensor above the renal region,^14,31,39 instead of relying on external anatomy landmarks. Two of these studies found an association between low RrSO₂ values and AKI, emphasizing the contribution of contamination of the NIRS signal by extrarenal tissues in acquiring reliable RrSO₂ measurements.¹⁸

In addition, the depth of the kidney beneath skin surface is dependent on the patient’s size and weight, and the average depth of penetration of NIRS sensors is generally around 2 cm in children. It is possible that if the kidney is located “too deep” (e.g., in overweight patients or older infants), the NIRS device may not be accurately measuring renal tissue oxygenation. Even if the renal cortex is reached by the near-infrared light, the renal medulla—physiologically more sensitive to hypoxia than the cortex⁵⁹—might remain out of the reach of renal region NIRS monitoring.

Diagnostic criteria used for diagnosing postoperative AKI were highly variable, reflected by the wide range of reported AKI incidences. It is possible that due to these differing criteria, the association between NIRS values and postoperative AKI may have been obscured. In pediatric patients we found some evidence for an association between RrSO₂ and novel biomarkers of kidney injury—mainly NGAL and cystatin C—suggesting that RrSO₂ might detect subtle alterations in renal function which may go undetected using conventional AKI criteria.

Strengths and Limitations

To the authors knowledge, this is the first systematic review about the use of perioperative RSO₂ to predict postoperative AKI in pediatric cardiac surgery. A certified information specialist helped develop a complete search strategy, which would unlikely develop selection bias. We performed a validated quality assessment of the selected studies and determined an inter-rater variability to objectify the differences in opinion. The heterogeneity of the included studies (regarding, for example, methodological differences in NIRS devices and the reporting of NIRS values, and the different AKI definitions used), prevented us from performing a meta-analysis, making this a descriptive review with a systematic search.

Advice for Future Research

In pediatric cardiac surgery, future studies on this topic should classify patients based on cardiac pathophysiology (cyanotic vs non-cyanotic).⁶⁰ The focus should be on the monitoring of RrSO₂ and RsSO₂ values, since they might predict postoperative AKI more consistently than RcSO₂. The proper positioning of NIRS sensors in the renal region should be guided by ultrasound imaging. The definition of RSO₂ thresholds could be based on deviations from individual RSO₂ baseline values rather than on absolute values, which might be less interpretable due to a wide variability in the population. The KDIGO criteria are currently advised in clinical practice³⁴ and should therefore be applied to detect AKI in future studies. We do not expect that the standardization of the population, monitoring and outcome in other observational studies will allow the definition of a single regional oxygenation threshold capable of predicting AKI, because of the multiple factors interplaying in determining kidney injury. It is likely that recommendations for threshold RSO₂ values will continue to rely primarily on consensus and expert opinions, rather than on consistent data from observational studies. We would suggest designing interventional studies to determine if a “NIRS-directed” respiratory and hemodynamic perioperative management could potentially reduce the incidence of postoperative AKI.

Conclusion

Across twenty studies conducted in pediatric patients undergoing cardiac surgery, no clear or consistent association was found between RSO₂ values and postoperative AKI. This currently precludes recommending the use of perioperative near-infrared spectroscopy monitoring as a reliable clinical tool for predicting postoperative acute kidney injury in this population.

Supplemental Material

Supplemental Material - Prognostic Value of Perioperative Near-Infrared Spectroscopy Monitoring for Postoperative Acute Kidney Injury in Pediatric Cardiac Surgery: A Systematic Review

Supplemental Material for Prognostic Value of Perioperative Near-Infrared Spectroscopy Monitoring for Postoperative Acute Kidney Injury in Pediatric Cardiac Surgery: A Systematic Review by Cornelia K. Niezen, Marco Modestini, Dario Massari, Arend F. Bos, Thomas W. L. Scheeren, Michel M. R. F. Struys, and Jaap Jan Vos in Seminars in Cardiothoracic and Vascular Anesthesia

Footnotes

Declaration of Conflicting Interests

The research group/department from M.M.R.F Struys received research grants and honoraria (paid to UMCG) from The Medicines Company (Parsippany, NJ, USA), Masimo (Irvine, CA, USA), Becton Dickinson (Eysins, Switzerland), Fresenius (Bad Homburg, Germany), Dräger (Lübeck, Germany), Paion (Aachen, Germany), Medtronic (Dublin, Ireland), Medcaptain Europe (Andelst, The Netherlands), for sponsor initiated research and consulting. T.W.L. Scheeren received research grants and honoraria from Edwards Lifesciences (Irvine, CA, USA) and Masimo Inc. (Irvine, CA, USA) for consulting and lecturing in the past (payments made to institution). TWLS is currently working as Senior Medical Director for BD Advanced Patient Monitoring (Heidelberg, Germany). The other authors declare no conflicts of interest.

Funding

The author(s) received no financial support for the research, authorship, and/or publication of this article.

ORCID iD

Cornelia K. Niezen

Supplemental Material

Supplemental material for this article is available online.

Appendix

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Supplementary Material

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Prognostic Value of Perioperative Near-Infrared Spectroscopy Monitoring for Postoperative Acute Kidney Injury in Pediatric Cardiac Surgery: A Systematic Review

Abstract

Introduction

Methods and Results

Conclusion

Keywords

Introduction

Methods

Search Strategy and Article Selection

Definitions of RSO2 Values

Data Extraction and Analysis

Results

Renal Region NIRS (RrSO2)

Cerebral NIRS (RcSO2)

Somatic NIRS (RsSO2)

Discussion

Key Findings

Study Population, Monitoring Site, and AKI Definition

Strengths and Limitations

Advice for Future Research

Conclusion

Supplemental Material

Supplemental Material - Prognostic Value of Perioperative Near-Infrared Spectroscopy Monitoring for Postoperative Acute Kidney Injury in Pediatric Cardiac Surgery: A Systematic Review

Footnotes

Declaration of Conflicting Interests

Funding

ORCID iD

Supplemental Material

Appendix

References

Supplementary Material

Definitions of RSO₂ Values

Renal Region NIRS (RrSO₂)

Cerebral NIRS (RcSO₂)

Somatic NIRS (RsSO₂)