Cerebral near-infrared spectroscopy (NIRS) for perioperative monitoring of brain oxygenation in children and adults

  • Protocol
  • Intervention

Authors


Abstract

This is the protocol for a review and there is no abstract. The objectives are as follows:

To assess the effects of perioperative cerebral NIRS monitoring and corresponding treatment strategies in adults and children, compared with no cerebral oxygenation monitoring or cerebral oxygenation monitoring based on non-NIRS technologies, on the detection of CDEs, neurological outcomes, non-neurological outcomes and socioeconomic impact (including cost of hospitalization and length of hospital stay).

Background

Description of the condition

The human brain is one of the organs with high oxygen utilization; thus it is extremely susceptible to hypoxic conditions (Gale 2004; Stys 1998). The incidence of intraoperative decrease in cerebral oxygen saturation is about 40% to 70%, depending on the definition of cerebral oxygen desaturation events (CDEs) and the patient population (Fischer 2011; Greenberg 2013; Murkin 2007; Slater 2009; Yao 2004). The prevalence of immediate postoperative CDEs is approximately 50% (Greenberg 2013). Potential contributors to low cerebral regional oxygen saturation (rScO2) include unstable haemodynamics, systemic desaturation, low hematocrit, hypocapnia, cardiac dysfunction, increased cerebral oxygen consumption, malposition of the head/cannula and specific surgical procedures such as deep hypothermic circulatory arrest and rewarming and aortic/carotid cross-clamping (Closhen 2013; Deschamps 2013; Harilall 2013; Hoffman 2004; Meng 2012; Moerman 2012; Morimoto 2003; Murkin 2009). Intraoperative CDEs were shown to correlate with increased risk of stroke, postoperative cognitive dysfunction (POCD), major organ morbidity or mortality and prolonged length of hospital stay (Monk 2008; Murkin 2007; Olsson 2006; Schön 2009; Slater 2009; Yao 2004). The hospital mortality of stroke patients after cardiac surgery is much higher than that of patients without stroke (19% vs 4%) (Salazar 2001). In paediatric patients, postoperative neurodevelopmental abnormalities were linked with perioperative CDEs in paediatric biventricular repair operations (Kussman 2010). Intervention for CDEs was shown to result in a decreased incidence of postoperative cognitive decline, less major organ morbidity or mortality and shortened intensive care unit and hospital stay following coronary artery bypass grafting (Murkin 2007; Slater 2009).

Description of the intervention

Successful intervention for perioperative cerebral ischaemia and hypoxia relies on early diagnosis (Ng 2011). Various modalities, including electroencephalogram (EEG), somatosensory evoked potential (SSEP), motor evoked potential (MEP), transcranial doppler (TCD), bispectral index (BIS), jugular bulb venous blood haemoglobin saturation (SjvO2) and biomarkers, have been adopted for this purpose with varying limitations (Andropoulos 2004; Guo 2011; Inoue 2013; Sanchez-Pena 2012; Williams 1994). Cerebral near-infrared spectroscopy (NIRS) is a relatively new addition to this list.

Near-infrared light (700 to 1000 nm) can penetrate through the superficial layers of the head, including the scalp and the skull, and can illuminate the cerebral tissue. The work by Jöbsis (Jobsis 1977) pioneered the use of NIRS to monitor rScO2. rScO2 is the percentage of oxy-haemoglobin over the sum of oxy- and deoxy-haemoglobin in pooled arterial, capillary and venous blood in the illuminated brain region. rScO2 is essentially determined by cerebral metabolic rate of oxygen (CMRO2) (demand) and oxygen delivery to the brain (supply). It can be altered by a change in volume percentage of cerebral arterial and/or venous blood (Kurth 1999; Watzman 2000; Yoshitani 2005). CDE treatment targets cerebral blood flow and arterial blood oxygen content augmentation, as well as anaesthetic depth increment. Variation exists among the intervention protocols adopted by previous studies (Ballard 2012; Goldman 2004; Murkin 2007). This may be due to differences in local practice style, types of surgery and patients' individual conditions. Cerebral NIRS has been used in cardiac and major vascular surgeries in both adults and children and in various non-cardiac surgeries but mainly in adults (Hirsch 2009).

Current cerebral oximetries used in the clinical setting are based on continuous-wave technology; newer technologies such as time-domain and frequency-domain NIRS are based on the transition from bench to bedside (Ferrari 2012; Watzman 2000). Although algorithm differences exist among continuous-wave devices used in patients, the fundamental principle is the same as that previously reviewed (Ferrari 2012; McCormick 1991; Murkin 2009). So far, five NIRS-based cerebral oximetries have been approved for patient use by the US Food and Drug Administration, including CerOx (Ornim, Inc., Dedham, Massachusetts, USA), EQUANOX 7600 and 8004CA (Nonin Medical, Inc., Plymouth, Minnesota, USA), FORE-SIGHT (CAS Medical Systems, Branford, Connecticut, USA) and INVOS (Somanetics Corporation, Troy, Michigan, USA). Examples of non-approved devices include NIMO (Nirox s.r.l., Brescia, Italy), NIRO-200NX and TRS-20 (Niro, Hamamatsu, Japan), Oxymon-II A and PortaLite (Artinis, Elst, Netherlands) and OxiplexTS (ISS, Champaign, Illinois, USA) (Ferrari 2012; Zheng 2013).

How the intervention might work

Clinical studies suggest that NIRS-based cerebral oximetry is reliable in detecting perioperative CDEs, especially in cardiac surgery (Bhatia 2007; Casati 2005; Egawa 2009; Greenberg 2013; Kussman 2010; Lovell 1999; Moreno 2013; Murkin 2007; Slater 2009). Various protocols aimed at CDE correction have been proposed (Scheeren 2012; Taillefer 2005). The refined algorithm has improved the accuracy of cerebral NIRS (Fischer 2008). Still, bias of NIRS-measured rScO2 exists interindividually and between different devices, likely because of differences in skin colour and gender and in the volume percentage of arterial and venous blood in the monitored brain region (Bickler 2013).

NIRS-measured rScO2 reflects the balance between cerebral oxygen consumption and supply. Differential diagnosis is needed when the cause of a change in rScO2 is deciphered. Denault et al. proposed an intervention algorithm for CDEs that involves increasing cerebral oxygen supply and/or decreasing consumption (Denault 2007). This algorithmic strategy has been recently tested by a prospective study that successfully used it to reverse decreased rScO2 in high-risk cardiac surgery in both the operating room and the intensive care unit (Deschamps 2013). The effort in applying cerebral NIRS in the perioperative setting is encouraged by the fact that NIRS is non-invasive, continuous and applicable at the patient's bedside. Nonetheless, whether a perioperative monitor can facilitate decision making to implement treatment strategies for reversal of cerebral desaturation, reduce adverse neurological events and improve overall outcomes in a cost-effective manner needs to be rigorously tested by randomized controlled trials (RCTs).

Why it is important to do this review

One of the fundamental goals of perioperative management is to avoid tissue ischaemia and hypoxia. This is especially true for vital organs such as the brain. It was shown that low rScO2 is associated with neurological injury under various cardiopulmonary bypass conditions in piglets (Anttila 2005; Hagino 2005). Several clinical studies in adults also demonstrated the association between intraoperative CDEs and adverse neurological outcomes, POCD, major organ morbidity or mortality and prolonged length of hospital stay (Monk 2008; Murkin 2007; Slater 2009; Vohra 2009; Yao 2004). In paediatric patients, cerebral NIRS seemed to correlate with vital parameters and enhance the prediction of neurodevelopmental outcomes after cardiac surgery (Kussman 2010; Menke 2014; Sood 2013). However, evidence supporting the predictive value of cerebral NIRS for adverse neurological outcome is low, and a very limited number of RCTs have tested the beneficial effect of cerebral NIRS on outcome in adult cardiac patients (Zheng 2013). Currently, the hypoxic threshold based on cerebral NIRS monitoring for intervention is poorly defined (Denault 2007; Fischer 2011; Murkin 2007; Orihashi 2004). In non-cardiac surgery, especially routine surgery under general anaesthesia, the role of cerebral NIRS is undefined (Ghosh 2012). Without well-defined outcomes from the use of NIRS and associated implemented treatment strategies, it is difficult to support the use of NIRS in the clinical setting (Hirsch 2010). In addition, cost-effectiveness analysis needs to be done to support the benefits of cerebral NIRS. Therefore, a critical, and up-to-date, review of the use of cerebral NIRS in the perioperative setting based on RCTs is pivotal not only in defining the areas where clarification or rigorous evidence is needed but also in guiding its application in the clinical setting.

Objectives

To assess the effects of perioperative cerebral NIRS monitoring and corresponding treatment strategies in adults and children, compared with no cerebral oxygenation monitoring or cerebral oxygenation monitoring based on non-NIRS technologies, on the detection of CDEs, neurological outcomes, non-neurological outcomes and socioeconomic impact (including cost of hospitalization and length of hospital stay).

Methods

Criteria for considering studies for this review

Types of studies

We will include all RCTs dealing with the use of cerebral NIRS in the perioperative setting (during the operation and within 72 hours after the operation), including the operating room (OR), the postanaesthesia care unit (PACU) and the intensive care unit (ICU). We will include all appropriate trials without regard for publication status or language used. We will also include quasi-randomized controlled trials, but we will conduct a sensitivity analysis of these studies. If any quasi-randomized trials greatly influence the findings of the review, greater resources will be deployed by contacting the trial authors, and the results would be interpreted with an appropriate degree of caution. We will exclude non-randomized trials such as cohort studies, which are susceptible to bias.

Types of participants

We will include adult participants (aged 18 years or older) and paediatric participants (aged younger than 18 years, excluding neonates) of both genders undergoing any types of surgeries under general anaesthesia. We will also include operations sometimes taken under local anaesthesia, such as carotid artery stenting and carotid endarterectomy. We will exclude neonates because another registered title is being conducted by the Cochrane Neonatal Group (Hyttel-Sorensen 2012).

Types of interventions

The intervention group will include all surgical participants who received cerebral NIRS monitoring and interventions correcting CDEs in the perioperative setting. So far, five NIRS-based cerebral oximetries have been approved by the US Food and Drug Administration (FDA). We will document the type of device used in each study and will carry out subgroup analyses.

The control group will include surgical participants monitored by conventional monitors (e.g. heart rate, mean arterial pressure) or other kinds of monitors such as electroencephalogram (EEG), transcranial doppler (TCD), bispectral index (BIS), jugular bulb oximetry, evoked potentials, cerebral tissue oxygen partial pressure (PbO2), etc. The control group will receive no monitoring by cerebral NIRS or monitoring, but the rScO2 readout will be concealed to the anaesthesiologist.

Types of outcome measures

Primary outcomes
  1. Postoperative stroke or other neurological injury, including adverse neurodevelopmental outcomes (within 24 hours postoperatively up to discharge or the end of follow-up). The diagnosis is based on new-onset neurological deficits, and findings are based on the neurological examination or neuroradiological evidence including computed tomography (CT), magnetic resonance imaging (MRI) or neuroangiogram. Neurological deficits will include abnormalities of sensory, motor, balance, speech, vision or autonomic nervous system functions.

  2. Postoperative delirium (POD) or POCD (within 24 hours postoperatively up to discharge). The diagnosis of POD or POCD is based on the criteria adopted by each qualified trial.

  3. Intraoperative mortality or postoperative mortality (at 24 hours, 30 days and one year after surgery).

Secondary outcomes

1. The occurrence of abnormal rScO2 during or after surgery: The definition may be attributed to the varying NIRS devices and differing physical and medical conditions of participants. We will use the criteria adopted by each included trial.

2. Any major non-neurological complications that occur during the intraoperative or postoperative period.

i. Respiratory insufficiency caused by pneumonia (fever, leukocytosis, chest x-ray or positive sputum culture), atelectasis (diagnosed based on chest x-ray), pulmonary emboli (sudden death confirmed by positive radiological findings) or pneumothorax (chest x-ray).

ii. Cardiovascular complications, including myocardial infarction (electrocardiogram (ECG) changes confirmed by abnormal myocardial enzymes), cardiac failure (clinical signs and symptoms or positive radiological findings), malignant arrhythmia (ECG changes) or cardiac arrest (ECG changes).

iii. Hepatic or renal insufficiency (clinical manifestations and laboratory evidence).

3. ICU length of stay.

4. Hospital length of stay.

5. Cost of hospitalization.

Search methods for identification of studies

Electronic searches

We will search the Cochrane Central Register of Controlled Trials (CENTRAL) (current issue), EMBASE (EMBASE.com) (1974 to date) and MEDLINE (PubMed) (1975 to date), with no language restrictions.

We will use search strategies to maximize sensitivity by following Section 6.4 of the Cochrane Handbook for Systematic Reviews of Interventions (Higgins 2011) to search for RCTs in EMBASE and PubMed. We will search CENTRAL, EMBASE and PubMed using the search terms described in Appendix 1, Appendix 2 and Appendix 3.

Searching other resources

We will scan the reference lists of all eligible articles and reviews.

For trials still ongoing, we will search the World Health Organization (WHO) international clinical trials registry platform, including clinicaltrials.gov, the metaRegister of Controlled Trials and other national trial registries. We will contact relevant specialists in this field to identify unpublished research and ongoing trials.

We will impose no language or region restrictions.

Data collection and analysis

Selection of studies

Two review authors (YY and KZ) will independently screen the results of searches and will record separately the reasons for inclusion/exclusion. We will exclude duplicate records. We will exclude studies in animal models. We will resolve disagreements on trial selection between review authors via discussion. If needed, we will consult with a third review author (RH or LM) to resolve disagreement. If further information is required, YY will contact the first author of the trial.

Data extraction and management

We will use a predesigned form (Appendix 4) to record the data obtained from included trials. Two review authors (YY and KZ) will independently extract data using a paper data extraction form (Appendix 4). We will resolve disagreements via discussion. If we are unable to reach a consensus, we will consult a third review author (RH or LM). If further information is needed, YY will contact the first author of the trial.

Assessment of risk of bias in included studies

Two review authors (YY and KZ) will independently assess the methodological quality of all included trials. We will try to resolve disagreements by discussion, and if a consensus cannot be reached, a third review author (LZ) will be consulted.

We will assess the risk of bias in included studies using the 'Risk of bias' tool that is described in Chapter 8 of the Cochrane Handbook for Systematic Reviews of Interventions (Higgins 2011). A copy of the assessment form that we adopt will be found in Appendix 4.

We will evaluate each trial according to selection bias, performance bias and attrition bias, including randomization and allocation concealment, blinding of participants, blinding of outcome assessment, missing data, selective reporting and any other bias. We will assess blinding separately for subjective (e.g. POCD) and objective (e.g. mortality) outcome measures. Objective outcome measures are less likely to be influenced by the knowledge of research personnel.

We will rate a trial as having 'low risk of bias' if all of the domains are assessed as adequate. We will rate a trial as having 'high risk of bias' if one or more of the domains are identified as inadequate or unclear. We will give reduced weight in the meta-analysis to trials with high risk of bias. We will perform sensitivity analyses to assess the influence of exclusion of 'high risk of bias' studies on the basis of results of the meta-analysis.

We will present a 'Risk of bias' table for each included study using the classification of 'low', 'high' or 'unclear' risk of bias. We will complete a 'Risk of bias' summary figure for each outcome to present a detailed description of all judgements made for all eligible studies in the review.

Measures of treatment effect

We will analyse categorical data using the Review Manager software (RevMan 5.1).

Dichotomous data

For dichotomous data, for example, whether cerebral NIRS is associated with postoperative neurological injury during the perioperative period, as well as a reduction in mortality at 24 hours, 30 days and one year, we will use a fixed-effect model or a random-effects model for analysis in accordance with the heterogeneity to estimate the overall risk ratio (RR) with the 95% confidence interval (CI).

Continuous data

For continuous data, such as length of ICU or hospital stay in days, we will use mean differences (MDs) as summary statistics in the meta-analysis.

Time-to-event data

We will perform survival analysis at 24 hours, 30 days and one year and will present the intervention effect as the hazard ratio with 95% CI. We will calculate the log hazard ratio and the variance using directly extracted individual patient data (IPD). If IPD cannot be extracted, we will estimate hazard ratios with 95% CIs from the survival curve or the survival rate.

Unit of analysis issues

We will include RCTs designed with a parallel group. We will treat cluster-randomized controlled trials (cluster-RCTs) appropriately. For cluster-RCTs, we will evaluate whether the data were correctly analysed, for example, if the analysis was performed at the identical level as the allocation (cluster level) or at a different level with appropriate statistical correction. If the data analysis was not correctly conducted, we will not include these trials in the meta-analysis because they may cause a unit of analysis error; however, we will comment on these data in the discussion.

Dealing with missing data

We (YY) will contact the original investigators to request missing data required for meta-analysis. The data are assumed missing at random, and we will analyse only the available data, as described in the Cochrane Handbook for Systematic Reviews of Interventions (Higgins 2011). We will perform sensitivity analyses to assess how sensitive results are to reasonable changes in our assumption. In the Discussion section, we will address the potential impact of missing data on the conclusions of the review.

Assessment of heterogeneity

We will appraise the heterogeneity of included trials based on both clinical diversity (e.g. type of surgery, type of anaesthesia, participants' comorbidities) and methodological diversity (risk of bias assessment). We will perform subgroup analysis and sensitivity analysis to address clinical heterogeneity, including performing visual inspection of the forest plot and determining the I2 statistic (Higgins 2011). We will consider an I2 statistic exceeding 50% to show high levels of heterogeneity, mandatings further analysis.

Assessment of reporting biases

We will conduct a funnel plot to qualitatively assess publication or reporting bias. To examine asymmetry of the funnel plot. We will perform a linear regression of effect estimates against their standard errors, weighted by the inverse of the variance of the intervention effect estimates, (Egger 1997) if more than 10 trials are included in the review.

Data synthesis

If the included studies do not have excessive clinical or statistical heterogeneity, we will use the Review Manager software to combine the data on population, interventions and outcomes and will perform a meta-analysis to generate a quantitative summary. The determination of whether a fixed-effect model or a random-effects model will be used depends on the degree of heterogeneity. If suitable numerical data are insufficient for a meta-analysis, we will carry out a narrative analysis for each study and will summarize all of the qualified data.

Subgroup analysis and investigation of heterogeneity

We will perform subgroup analyses as follows, including subgroups of participants and interventions.

Subgroups of participants
Subgroup analysis according to type of surgery
  1. Participants undergoing craniotomy.

  2. Participants undergoing cardiac or great vessel surgery
    with/without bypass.

  3. Participants undergoing carotid endarterectomy.

  4. Participants undergoing other surgery.

Subgroup analysis according to age of participants
  1. Adults (> or = 18 years old).

  2. Children (< 18 years old).

Subgroups of interventions
  1. Perioperative cerebral NIRS monitoring versus no cerebral oxygenation monitoring.

  2. Perioperative cerebral NIRS monitoring versus other kinds of cerebral oxygenation monitoring.

Subgroup analysis according to documentation of device types
  1. INVOS (Somanetics Corporation, Troy, Michigan, USA).

  2. CerOx (Ornim, Inc., Dedham, Massachusetts, USA).

  3. EQUANOX 7600 (Nonin Medical, Inc., Plymouth, Minnesota, USA).

  4. EQUANOX 8004CA (Nonin Medical, Inc., Plymouth, Minnesota, USA).

  5. FORE-SIGHT (CAS Medical Systems, Branford, Connecticut, USA).

Sensitivity analysis

We will carry out sensitivity analyses to assess the effects of trial quality by excluding each trial sequentially and will exclude trials at high risk of bias, which are inadequate in allocation of concealment. We will use a random-effects model and a fixed-effect model separately for each outcome variable.

Summary of findings

We will use the principles of the GRADE system (Guyatt 2008) to assess the quality of the body of evidence associated with the specific outcomes (rate of postoperative stroke or other neurological injury, POD, POCD or mortality at 24 hours, 30 days and one year) in our review and will construct a 'Summary of findings' (SoF) table using the GRADE software.

The GRADE approach evaluates the quality of a body of evidence based on the extent to which one can be confident that an estimate of effect or association reflects the item being assessed. The quality of a body of evidence considers risk of bias (methodological quality), directness of the evidence, heterogeneity of the data, precision of effect estimates and risk of publication bias.

Acknowledgements

We thank Jane Cracknell (Managing Editor, Cochrane Anaesthesia Review Group) and Karen Hovhannisyan (Trials Search Co-ordinator, Cochrane Anaesthesia Review Group) for their assistance during the preparation of this protocol. We would like to thank Mathew Zachrias and Anna Lee (Content Editors); Cathal Walsh (Statistical Editor); Dolores Matthews (Copy Editor); and Federico Bilotta, Jennifer C Hirsch-Romano, Miguel F Arango and Arnab Ghosh (Peer Reviewers) for their help and editorial advice during the preparation of this protocol for the systematic review. We also thank Jun Xia (Research Assistant, Cochrane Schizophrenia Group) for her help in the preparation of this protocol for the review.

Appendices

Appendix 1. CENTRAL search strategy

#1 head or crania* or craniocerebral or capitis or craniu* or cerebra* or cerebru* or brain* or forebrain* or skull* or hemispher* or intracran* or encephal*:ti,ab,kw

#2 (oxygen saturation*) or oximetr* or oxygenati* or ScO2:ti,ab,kw

#3 MeSH descriptor: [Oximetry] explode all trees

#4 #2 or #3

#5 #1 and #4

#6 (near-infrared spectromet*) or (near-infrared spectroscop*) or (spectroscop*, near-infrared) or (NIR spectroscop*) or (spectroscop*, NIR) or (spectromet*, near-infrared)

#7 MeSH descriptor: [Spectroscopy, Near-Infrared] explode all trees

#8 #5 or #6 or #7

#9 operati* or perioperat* or peroperat* or preoperati* or postoperat* or intraoperat* or surg* or (anesthe* recovery)

#10 MeSH descriptor: [Perioperative Care] explode all trees

#11 MeSH descriptor: [Perioperative Nursing] explode all trees

#12 MeSH descriptor: [Specialties, Surgical] explode all trees

#13 #9 or #10 or #11 or #12

#14 #8 and #13

#15 MeSH descriptor: [Models, Animal] explode all trees

#16 MeSH descriptor: [Animals] explode all trees

#17 MeSH descriptor: [Animal Experimentation] explode all trees

#18 MeSH descriptor: [Disease Models, Animal] explode all trees

#19 MeSH descriptor: [Animals, Laboratory] explode all trees

#20 MeSH descriptor: [Humans] explode all trees

#21 MeSH descriptor: [Infant, Newborn] explode all trees

#22 (newborn infant*) or newborn* or neonate*:ti,ab,kw

#23 #15 or #16 or #17 or #18 or #19

#24 #21 or #22

#25 #23 not #20

#26 #14 not #25

#27 #26 not #24

Appendix 2. EMBASE (EMBASE.com) search strategy

#1 'head'/exp OR head OR crania* OR craniocerebral OR capitis OR craniu* OR cerebra* OR cerebru* OR brain* OR forebrain* OR skull* OR hemispher* OR intracran* OR encephal*:ab,ti

#2 oxygen NEAR/3 saturation* OR oximetr* OR oxygenati* OR sco2:ab,ti

#3 'oximetry'/exp

#4 #2 OR #3

#5 #1 AND #4

#6 'near infrared spectroscopy'/exp

#7 (near-infrared AND spectromet*) OR (near-infrared AND spectroscop*) OR (NIR AND spectroscop*):ab,ti

#8 #5 OR #6 OR #7

#9 operati* OR perioperat* OR peroperat* OR preoperati* OR postoperat* OR intraoperat* OR surg* OR (anesthe* NEAR/3 recovery):ab,ti

#10 'perioperative period'/exp

#11 'perioperative nursing'/exp

#12 'perioperative complication'/exp

#13 'surgery'/exp

#14 #9 OR #10 OR #11 OR #12 OR #13

#15 'randomized controlled trial'/exp

#16 'randomized controlled trial' OR 'randomized controlled trial':ab,ti

#17 random*:ab,ti

#18 'randomization'/exp

#19 'controlled clinical trial'/exp

#20 'clinical trial'/exp

#21 'multicenter study'/exp

#22 multicent*:ab,ti

#23 'phase 4 clinical trial'/exp

#24 'double blind procedure'/exp

#25 'single blind procedure'/exp

#26 random* OR cross?over* OR factorial* OR placebo* OR volunteer*:ab,ti

#27 singl*:ab,ti OR doubl*:ab,ti OR trebl*:ab,ti OR tripl*:ab,ti AND (blind*:ab,ti OR mask*:ab,ti)

#28 randomized:ab,ti OR randomized:ab,ti OR randomly:ab,ti OR 'random order':ab,ti OR 'random sequence':ab,ti OR 'random allocation':ab,ti OR 'randomly allocated':ab,ti OR 'at random':ab,ti OR 'randomized controlled trial':ab,ti OR 'controlled clinical trial':ab,ti

#29 #15 OR #16 OR #17 OR #18 OR #19 OR #20 OR #21 OR #22 OR #23 OR #24 OR #25 OR #26 OR #27 OR #28

#30 'human'/exp

#31 'animal'/exp OR 'nonhuman'/exp OR 'experimental animal'/exp OR 'animal experiment'/exp OR 'animal model'/exp OR 'disease model'/exp

#32 rat*:ab,ti OR rodent*:ab,ti OR animal*:ab,ti OR mice:ab,ti OR murin*:ab,ti OR dog*:ab,ti OR canine*:ab,ti OR cat*:ab,ti OR feline*:ab,ti OR rabbit*:ab,ti OR pig*:ab,ti

#33 'newborn'/exp

#34 newborn NEAR/3 infant* OR newborn* or neonate*:ab,ti

#35 #33 OR #34

#36 #31 OR #32

#37 #36 NOT #30

#38 #29 NOT #37

#39 #38 NOT #35

#40 #8 AND #14 AND #39

Appendix 3. MEDLINE (PubMed) search strategy

#1 (randomized or randomized or randomly or random order or random sequence or random allocation or randomly allocated or at random or randomized controlled trial)[pt]

#2 controlled clinical trial[pt]

#3 randomized controlled trials as Topic[mh]

#4 double-blind method[mh]

#5 single-blind method[mh]

#6 clinical trials as topic[mh]

#7 placebos[mh]

#8 random*[tiab]

#9 (singl* or doubl* or trebl* or tripl*) and (blind* or mask*)

#10 clinical trial*[tiab]

#11 placebo*[tiab]

#12 #1 or #2 or #3 or #4 or #5 or #6 or #7 or #8 or #9 or #10 or #11

#13 models, animal[mh]

#14 animals[mh]

#15 animal experimentation[mh]

#16 disease models, animal[mh]

#17 animals, laboratory[mh]

#18 humans[mh]

#19 infant, newborn[mh]

#20 (newborn infant*) or newborn* or neonate*[tiab]

#21 #13 or #14 or #15 or #16 or #17

#22 #19 or #20

#23 #21 not #18

#24 #12 not #23

#25 #24 not #22

#26 head or crania* or craniocerebral or capitis or craniu* or cerebra* or cerebru* or brain* or forebrain* or skull* or hemispher* or intracran* or encephal*[tiab]

#27 (oxygen saturation*) or oximetr* or oxygenati* or ScO2[tiab]

#28 oximetry[mh]

#29 #27 or #28

#30 #26 and #29

#31 (near-infrared spectromet*) or (near-infrared spectroscop*) or (spectroscop*, near-infrared) or (NIR spectroscop*) or (spectroscop*, NIR) or (spectromet*, near-infrared)

#32 spectroscopy, near-infrared[mh]

#33 #30 or #31 or #32

#34 operati* or perioperat* or peroperat* or preoperati* or postoperat* or intraoperat* or surg* or (anesthe* recovery)

#35 perioperative care[mh]

#36 perioperative nursing[mh]

#37 specialties, surgical[mh]

#38 #34 or #35 or #36 or #37

#39 #25 and #33 and #38

Appendix 4. Data collection form

CARG

Data collection form

Intervention review—RCTs only

Review title or ID
Cerebral near-infrared spectroscopy (NIRS) for perioperative monitoring of oxygenation in children and adults
Study ID (surname of first author and year first full report of study was published e.g. Smith 2001)
     
Report IDs of other reports of this study (e.g. duplicate publications, follow-up studies)
     

Notes:        

 

 

1.     General information

 

Date form completed (dd/mm/yyyy)      
Name/ID of person extracting data

     

 

Report title

(title of paper/abstract/report from which data are extracted)

     

 

Report ID

(ID for this paper/abstract/report)

     

 

Reference details

 

     

 

 

Report author contact details

     

 

Publication type

(e.g. full report, abstract, letter)

     

 

Study funding sources

(including role of funders)

     

 

Possible conflicts of interest

(for study authors)

     

 

Notes:      

 

 

 

2.     Study eligibility

 

Study characteristics

Eligibility criteria

(Insert eligibility criteria for each characteristic as defined in the Protocol)

Yes/ NO/

Unclear

Location in text
Type of study

Randomized controlled trial

Controlled clinical trial

(quasi-randomized trial)

  
Type of study participants

Relevant participants

Adult participants: aged 18 years or older

Paediatric participants: younger than 18 years of age, excluding neonates

Perioperative period

  
Types of interventions

Relevant interventions

Cerebral NIRS monitoring and intervention correcting CDEs in the perioperative setting

Control group: conventional monitors (e.g. heart rate, mean arterial pressure) or other kinds of monitors such as EEG, TCD, BIS, jugular bulb oximetry, evoked potentials, cerebral tissue oxygen partial pressures (PbO2), etc., either not monitored by cerebral NIRS or monitored but with the rScO2 readout concealed to anaesthesiologists

  
Types of outcome measures

Relevant outcomes

Postoperative neurological injury, postoperative delirium or cognitive dysfunction, mortality

The occurrence of abnormal rScO2 during or after surgery; any major non-neurological complications that occur during the intraoperative or postoperative period; hospital length of stay or intensive care length of stay; cost of hospitalization

  
Reason for exclusion INCLUDEEXCLUDE  
Notes:   

 

DO NOT PROCEED IF STUDY EXCLUDED FROM REVIEW

3.     Population and setting

 

 

Description

Include comparative information for each group (i.e. intervention and control) if available

Location in text

Population description

(from which study participants are drawn)

          

Setting

(including location and social context)

          
Inclusion criteria          
Exclusion criteria          
Method/s of recruitment of participants          

Informed consent obtained

 

          

Yes     No    Unclear

          
Notes:         

 

4.     Methods

 

  Descriptions as stated in report/paper  Location in text

Aim of study

 

 

          
Design (e.g. parallel, cross-over, cluster)          

Unit of allocation

(by individuals, cluster/groups or body parts)

          

Start date

 

     

 

     

End date

 

     

 

     

Total study duration

 

          
Ethical approval needed/obtained for study

          

Yes     No    Unclear

          

Notes:    

 

 

5.     Risk of bias assessment

See Chapter 8 of the Cochrane Handbook for Systematic Reviews of Interventions (Higgins 2011)

 

Domain Risk of bias 

Support for judgement

 

Location in text
Low riskHigh riskUnclear

Random sequence generation

(selection bias)

             

Allocation concealment

(selection bias)

 

             

Blinding of participants

(performance bias)

   

Outcome group: all/     

     

     
(if required)   

Outcome group:      

     

     

Blinding of outcome assessment

(detection bias)

   

Outcome group: all/     

     

     
(if required)   

Outcome group:      

     

     

Incomplete outcome data

(attrition bias)

 

             

Selective outcome reporting?

(reporting bias)

             

Other bias

 

 

             

Notes:        

 

 

 

6.     Participants

Provide overall data and, if available, comparative data for each intervention or comparison group.

 

  Description as stated in report/paper Location in text

Total no. randomly assigned

(or total pop. at start of study for NRCTs)

          

Clusters

(if applicable, no., type, no. people per cluster)

          
Baseline imbalances          

Withdrawals and exclusions

(if not provided below by outcome)

          
Age          
Sex          
American Society of Anesthesiologists (ASA) grade          

Comorbidities

 

          
Treatment received for comorbidities          
Surgery type          
Length of surgery  

Subgroups measured

 

          

Subgroups reported

 

          

Notes:        

 

 

 

7.     Intervention groups

Copy and paste table for each intervention and comparison group

 

Intervention group (NIRS group)

  Description as stated in report/paper Location in text
Group name  

No. randomly assigned to group

(specify whether no. people or clusters)

  
Theoretical basis (include key references)  
Description (include sufficient detail for replication, e.g. content, dose, components)  
Duration of NIRS monitoring  
Timing of NIRS monitoring (in OR, PACU or ICU)  
Baseline of cerebral oxygenation  
Episode and duration of decline in rScO2  
Treatment of decline in rScO2  
Delivery of anaesthetic agents (whether TIVA, inhalational agents or both)  
Economic variables
(i.e. intervention cost, changes in other costs as result of intervention)
  
Notes:

 

Control group 1 (No cerebral oxygenation monitoring group)

  Description as stated in report/paper Location in text
Group name  

No. randomly assigned to group

(specify whether no. people or clusters)

  
Theoretical basis (include key references)  
Description (include sufficient detail for replication, e.g. content, dose, components)  
Delivery of anaesthetic agents (whether TIVA, inhalational agents or both)  
Economic variables
(i.e. intervention cost, changes in other costs as result of intervention)
  
Notes:

Control group 2 (Non-NIRS cerebral monitoring group)

  Description as stated in report/paper Location in text
Group name  

No. randomly assigned to group

(specify whether no. people or clusters)

  
Theoretical basis (include key references)  
Description (include sufficient detail for replication, e.g. content, dose, components)  
Duration of cerebral monitoring  
Timing of cerebral monitoring (in OR, PACU or ICU)  
Baseline of cerebral oxygenation  
Episode and duration of decline in cerebral oxygenation  
Treatment of decline in cerebral oxygenation  
Delivery of anaesthetic agents (whether TIVA, inhalational agents or both)  
Economic variables
(i.e. intervention cost, changes in other costs as result of intervention)
  
Notes:
8.     Outcomes

Copy and paste table for each outcome.

 

Outcome 1

  Description as stated in report/paper Location in text
Outcome name: postoperative stroke or other neurological injury, including adverse neurodevelopmental outcomes  
Time points measured: within 24 hours postoperatively up to discharge or the end of follow-up  
Time points reported  

Outcome definition

YES/NO

  
Person measuring/reporting  

Unit of measurement

(if relevant)

  
Is outcome/tool validated?Yes No Unclear  
Imputation of missing data
(e.g. assumptions made for ITT analysis)
  
Power  
Notes:

 

Outcome 2

  Description as stated in report/paper Location in text
Outcome name: POD or POCD  
Time points measured: within 24 hours postoperatively up to discharge  
Time points reported  

Outcome definition

YES/NO

  
Person measuring/reporting  

Unit of measurement

(if relevant)

  
Is outcome/tool validated?Yes No Unclear  
Imputation of missing data
(e.g. assumptions made for ITT analysis)
  
Power  
Notes:

Outcome 3

  Description as stated in report/paper Location in text
Outcome name: intraoperative or postoperative mortality  
Time points measured: during surgery or at 24 hours, 30 days and one year after surgery  
Time points reported  

Outcome definition

YES/NO

  
Person measuring/reporting  

Unit of measurement

(if relevant)

  
Is outcome/tool validated?Yes No Unclear  
Imputation of missing data
(e.g. assumptions made for ITT analysis)
  
Power  
Notes:

Outcome 4

  Description as stated in report/paper Location in text
Outcome name: occurrence of abnormal rScO2 during or after surgery  
Time points measured: during surgery or within 72 hours after surgery  
Time points reported  

Outcome definition

YES/NO

  
Person measuring/reporting  

Unit of measurement

(if relevant)

  
Is outcome/tool validated?Yes No Unclear  
Imputation of missing data
(e.g. assumptions made for ITT analysis)
  
Power  
Notes:

Outcome 5

  Description as stated in report/paper Location in text
Outcome name: any major non-neurological complications that occur during intraoperative or postoperative period  
Time points measured: during surgery or within 24 hours postoperatively up to discharge  
Time points reported  

Outcome definition

YES/NO

  
Person measuring/reporting  

Unit of measurement

(if relevant)

  
Is outcome/tool validated?Yes No Unclear  
Imputation of missing data
(e.g. assumptions made for ITT analysis)
  
Power  
Notes:

Outcome 6

  Description as stated in report/paper Location in text
Outcome name: length of ICU or hospital stay (in days)  
Time points measured: at discharge from ICU or hospital  
Time points reported  

Outcome definition

YES/NO

  
Person measuring/reporting  

Unit of measurement

(if relevant)

  
Is outcome/tool validated?Yes No Unclear  
Imputation of missing data
(e.g. assumptions made for ITT analysis)
  
Power  
Notes:

Outcome 7

  Description as stated in report/paper Location in text
Outcome name: cost of hospitalization  
Time points measured: at discharge from hospital  
Time points reported:  
Outcome definition: mean difference in cost of hospitalization
in US dollar/UK sterling between NIRS group and control group
  
Person measuring/reporting  

Unit of measurement

(if relevant)

  
Is outcome/tool validated?Yes No Unclear  
Imputation of missing data
(e.g. assumptions made for ITT analysis)
  
Power  
Notes:
9.     Results

Copy and paste the appropriate table for each outcome, including additional tables for each time point and subgroup as required.

 

Dichotomous outcome

  Description as stated in report/paper   Location in text
Comparison          
Outcome          
Subgroup          
Time point
(specify whether from start or end of intervention)
          
Results Intervention Comparison     
No. eventsNo. participantsNo. eventsNo. participants
                    
No. missing participants and reasons               
No. participants moved from other group and reasons               
Any other results reported          
Unit of analysis (by individuals, cluster/groups or body parts)           

Statistical methods used and appropriateness of these methods

(e.g. adjustment for correlation)

          
Reanalysis required? (specify)

          

Yes     No    Unclear

          
Reanalysis possible?

          

Yes     No    Unclear

          
Reanalysed results          
Notes:         

 

10. Applicability

 

Have important populations been excluded from the study?

(consider disadvantaged populations and possible differences in the intervention effect)

Yes     No    Unclear 

Is the intervention likely to be aimed at disadvantaged groups?

(e.g. .lower socioeconomic groups)

Yes     No    Unclear     

Does the study directly address the review question?

(any issues of partial or indirect applicability)

Yes     No    Unclear     
Notes:        

 

11. Other information

 

  Description as stated in report/paper Location in text
Key conclusions of study authors           
References to other relevant studies           
Correspondence required for further study information (from whom, what and when) 
Notes:         

Contributions of authors

Yun Yu (YY), Kaiying Zhang (KZ), Ling Zhang (LZ), Ruquan Han (RH), Huantao Zong (HZ), Lingzhong Meng (LM)

Conceiving of the review: YY, RH

Co-ordinating the review: YY, KZ, LZ, RH

Undertaking manual searches: HZ

Screening search results: YY, KZ

Organizing retrieval of papers: YY, KZ, RH

Screening retrieved papers against inclusion criteria: YY, KZ

Appraising quality of papers: YY, KZ, LZ, LM

Abstracting data from papers: YY, KZ

Writing to authors of papers to request additional information: YY

Providing additional data about papers: YY, KZ, HZ

Obtaining and screening data on unpublished studies: YY, KZ, HZ

Providing data management for the review: YY, KZ, LZ

Entering data into Review Manager (RevMan 5.1): YY, KZ

Handling RevMan statistical data: YY, LZ

Performing other statistical analysis not using RevMan: KZ, LZ

Interpreting data: YY, KZ, LZ, RH, LM

Making statistical inferences: LZ

Writing the review: YY, KZ, LZ, RH, LM

Securing funding for the review: N/A

Performing previous work that was the foundation of the present study: YY, KZ

Serving as guarantor for the review (one author): RH

Taking responsibility for reading and checking the review before submission: YY, LM

Declarations of interest

Yun Yu: none known.

Kaiying Zhang: none known.

Ling Zhang: none known.

Ruquan Han: none known.

Huantao Zong: none known.

Lingzhong Meng: none known.

Sources of support

Internal sources

  • Capital Medical University, China.

External sources

  • No sources of support supplied

Ancillary