literature review on cardiac surgery

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• v.100(15); 2021 Apr 16

A systematic review and meta-analysis of the effects of early mobilization therapy in patients after cardiac surgery

a The Affiliated People's Hospital of Fujian University of Traditional Chinese Medicine

b National Clinical Research Base of Traditional Chinese Medicine, Fuzhou 350004, Fujian Province

c Yunnan University of Traditional Chinese Medicine, Kunming 650500, Yunnan Province, China.

Lianghua Chen

Zhichen lin, xiaofang you, xinyi zheng, wanqing lin, background:.

Prolonged hospitalization and immobility of critical care patients elevate the risk of long-term physical and cognitive impairments. However, the therapeutic effects of early mobilization have been difficult to interpret due to variations in study populations, interventions, and outcome measures. We conducted a meta-analysis to assess the effects of early mobilization therapy on cardiac surgery patients in the intensive care unit (ICU).

PubMed, Excerpta Medica database (EMBASE), Cumulative Index of Nursing and Allied Health Literature (CINAHL), Physiotherapy Evidence Database (PEDro), and the Cochrane Library were comprehensively searched from their inception to September 2018. Randomized controlled trials were included if patients were adults (≥18 years) admitted to any ICU for cardiac surgery due to cardiovascular disease and who were treated with experimental physiotherapy initiated in the ICU (pre, post, or peri-operative). Data were extracted by 2 reviewers independently using a pre-constructed data extraction form. Length of ICU and hospital stay was evaluated as the primary outcomes. Physical function and adverse events were assessed as the secondary outcomes. Review Manager 5.3 (RevMan 5.3) was used for statistical analysis. For all dichotomous variables, relative risks or odds ratios with 95% confidence intervals (CI) were presented. For all continuous variables, mean differences (MDs) or standard MDs with 95% CIs were calculated.

The 5 studies with a total of 652 patients were included in the data synthesis final meta-analysis. While a slight favorable effect was detected in 3 out of the 5 studies, the overall effects were not significant, even after adjusting for heterogeneity.

Conclusions:

This population-specific evaluation of the efficacy of early mobilization to reduce hospitalization duration suggests that intervention may not universally justify the labor barriers and resource costs in patients undergoing non-emergency cardiac surgery.

PROSPERO Research registration identifying number:

CRD42019135338.

1. Introduction

Prolonged intensive care hospitalization has been linked to increased morbidity and long-term mortality after hospital discharge. [ 1 ] It has been estimated that up to 46% of intensive care unit (ICU) patients acquire intensive care unit-acquired weakness (ICU-AW) during their stay. [ 2 ] ICU-AW includes polyneuropathy, myopathy, and/or muscular atrophy which can prolong immobilization and inhibit long-term physical and cognitive function. [ 3 ] Early physical rehabilitation has been associated with improved physical function and is recommended for ICU patients by the European Society of Intensive Care Medicine. [ 1 ] While independent studies have reported a variety of benefits of early mobilization therapy, including reduced mechanical ventilation days, reduced hospital length of stay, and functional outcomes, [ 4 ] various reviews have confirmed only the short-term benefits of early mobilization intervention, calling into question whether the high resource and labor costs offset these short-term benefits. [ 5 ]

Other reviews of early mobilization therapy in critically ill patients have yielded conflicting findings, with either no or inconsistent effects on functional recovery, quality of life, length of ICU or total hospitalization stay, and long or short-term mortality. [ 6 , 7 ] Conflicting findings may be due to several factors including intervention differences, variations in reporting, quality of available resources, etc. Moreover, it should be noted that some systematic reviews have entirely deemed the current body of literature suboptimal for comparison due to lack of consistency or reliability in the delivered intervention. [ 8 ] For example, Reid et al [ 8 ] report that out of 117 studies evaluated, none reported the same intervention in exactly the same way. Thirty-seven percent did not report intervention start time and 26% did not report overall intervention duration, limiting understanding and generalizability of the interventions. Another potentially confounding factor is the variety of patient populations (and acuities) evaluated across studies of ICU early mobilization, which often include patients admitted for cardiac disease, respiratory illness, and acquired brain injury, among other critical illnesses. Toward the aim of improving homogeneity of patient populations, an increasing number of targeted studies are being undertaken.

It has been reported that 58% of cardiac surgery patients are vulnerable to post-operative complications and subsequent delays in hospital discharge and functional recovery. While currently, early mobilization and prophylactic respiratory physiotherapy are post-operatively prescribed for cardiac surgery patients, no consensus exists regarding optimal mobility protocols nor how these interventions impact hospitalization duration, post-operative complications, or functional recovery of cardiac surgery patients specifically.

To address the lack of conclusive evidence of the effect of early mobilization on cardiac surgery patients in critical care settings, this systematic review and meta-analysis aimed to evaluate randomized controlled trials exclusively evaluated in cardiac surgery patients treated experimentally with early mobilization.

2.1. Study design

This systematic review of randomized controlled trials (RCTs) was performed to evaluate the effects of early mobilization therapy on cardiac surgery patients in the ICU. We followed the Preferred Reporting Items of Systematic Reviews and Meta-Analyses (PRISMA) guidelines (see Supplementary Checklist).

2.2. Search strategy

The following databases were used to search for relevant keywords: PubMed, Excerpta Medica database (EMBASE), Cumulative Index of Nursing and Allied Health Literature (CINAHL), Physiotherapy Evidence Database (PEDro), and the Cochrane Library from inception to September 20, 2018 (Table ​ (Table1). 1 ). Two independent investigators (XY and DD) screened titles, keywords, and abstracts for relevant indicators and abbreviated adherence to inclusion/exclusion criteria. If a publication cited other relevant titles not already identified by the initial search strategy, effort was made to track down and screen those titles. A second, full-text screening of all qualifying entries was subsequently performed according the criteria listed below. Effort was taken during screening to identify and mitigate potential sources of publication bias such as the independent assessment of a randomized controlled trial based on methodology rather than claim or title and the inclusion of qualifying cardiac populations included in larger intensive care unit studies, where the cardiac population could be extracted from the data set. However, factors inherent to randomized trials such as the bias of publication of positive findings as well as our exclusion of studies published in non-English languages should be considered.

Electronic search strategy in different databases.

2.3. Methodological quality assessment

A methodological quality assessment of studies was performed by 2 investigators (XZ and DL) independently using the PEDro scale. [ 9 ] The PEDro scale has demonstrated acceptable validity and reliability among physiotherapy trials [ 10 ] and was selected due to its high interrater reliability and strong convergence with the Cochrane Back and Neck (CBN) risk of bias tool. [ 11 , 12 ] The scale evaluates 11 items including: inclusion criteria and source, random allocation, concealed allocation, similarity at baseline, subject blinding, therapist blinding, assessor blinding, completeness of follow up, intention-to-treat analysis, between-group statistical comparisons, and point measures and variability . Each item is rated as either a “yes” or “no” and the total PEDro score is tallied by the total number of “yes” items (excluding the inclusion criteria and source item). In a few instances, discrepancies regarding study qualification or methodological quality scores were resolved between investigators by discussion after scores/lists had been generated independently. In these cases the authors worked together to come to an agreement on inclusion/exclusion or quality score.

2.4. Participants

The authors included studies of adult patients (≥18 years) admitted to any ICU for cardiac surgery due to cardiovascular disease and who were treated with experimental physiotherapy initiated in the ICU (pre, post, or peri-operative).

2.5. Interventions and comparators

Interventions could include passive or active exercises, strengthening exercises, cycling, progressive mobility, or any combination thereof. Studies were included only if a comparator group included either no prescribed mobilization intervention or delayed intervention (i.e., intervention prescribed after ICU discharge).

Studies which included only a portion of patients admitted for cardiac disease-related events were excluded. Studies including patients admitted for myocardial infarction or other emergency cardiac surgery were excluded as these populations are typically prescribed mobile restriction to reduce cardiac overload. Massage and electro-muscular stimulation studies were not included. Additionally, we excluded studies where intervention was initiated after ICU discharge, or consisted mainly of chest physiotherapy, or other respiratory interventions (i.e., inspiratory training). Likewise, table tilt or vibration-capable bed interventions were excluded. Studies which relied on self-monitored, self-initiated, or self-reported mobility therapy and/or metrics of mobility were excluded. Intervention protocol studies, safety and feasibility studies, editorials, reviews, surveys of practice, retrospective, non-randomized, and non-English studies were also excluded. Studies were excluded if they did not report at minimum the duration of total hospitalization. Finally, studies where comparator included variations in physiotherapy (intensity, frequency, or duration) rather than a true control (delayed or no intervention) group were also excluded.

2.6. Outcomes

Primary outcomes: Hospital length of stay and ICU length of stay.

Secondary outcomes: Physical Function and Adverse Events.

Physical function in this review was defined as any supervised assessment of ambulation or mobility as well as the administration of questionnaires of physical capacity such as the physical portion of the short form (SF-36), a generalized quality of life survey. In this review adverse events were defined as was defined as any occurrence threatening the stability or eligibility for inclusion of the patient including, myocardial infarct, hospital mortality, formation of pressure ulcers/hematomas, etc. Primary outcomes were measured based on hospital admission and discharge records. Due to the variable nature of the intervention, which could be pre-, peri-, or post-operative (ranging from a single session to months of recurring physiotherapy), secondary outcomes were assessed at varying intervals.

2.7. Data synthesis and analysis

Data were extracted by 2 reviewers (XZ and DL) independently using a pre-constructed data extraction form. The data extraction form included the publication information (title, authors, year, etc), participant characteristics (age, gender, etc), intervention details (intervention of experimental group and intervention of control group, frequency, intensity, duration, follow-up), outcomes (primary outcome and secondary outcome, outcome instruments), and study design (randomized, blinded, etc). For continuous data, standard deviation (SD) or standard error (SE) values were extracted. For categorical data, the number of events was extracted.

Review Manager 5.3 (RevMan 5.3) was used for statistical analysis. For all dichotomous variables, relative risks or odds ratios with 95% confidence intervals (CI) were presented. For all continuous variables, mean differences (MDs) or standard MDs with 95% CIs were calculated. Two-sided P value of <.05 was defined as statistical significance. The fixed-effect model was used if data were available and there was no significant heterogeneity. If heterogeneity was high ( I 2  > 75%), the pooled analysis was not considered and a sensitivity analysis was performed. The χ 2 test and Higgins I 2 value were used to assess statistical heterogeneity, with I 2  > 75% suggesting high statistical heterogeneity. [ 13 ] In some evaluations, studies were excluded on the basis of clinical heterogeneity to determine the study's influence on the pooled effect size.

2.8. Participant and public involvement

No patients were involved in this study.

2.9. Ethical consideration

Institutional review board approval was not necessary because all the data were retrieved from public databases.

3.1. Study selection

The search among all databases included in this systematic review yielded 1100 and 10 additional studies were identified through other sources. One thousand and fifty studies underwent expedited screening (after removal or duplicates) which included mining summaries and abstracts for compatibility with inclusion/exclusion criteria. After expedited screening, 98 studies were reviewed in full. In 39 studies, the cardiac disease population of interest was either not represented in the pool of critically ill patients or was mixed with patients admitted for non-cardiac critical illness or unspecified. In 35 studies, the intervention did not meet the inclusion criteria, in 13 studies the clinical intervention was not initiated in an ICU, and in 5 studies the comparator group was deemed incompatible with outlined criteria. Ultimately, 5 studies were included in the data synthesis final meta-analysis (Fig. ​ (Fig.1 1 ).

Flowchart for the identification of studies used in the systematic review and meta-analysis of early mobilization interventions in patients undergoing cardiac surgery.

3.2. Methodological quality

Methodological quality based on the PEDro scale revealed an average study score of 5.8 (Table ​ (Table2). 2 ). Three out of 5 included randomized trials included concealment of randomized allocation. All included studies included subjects that were comparable at baseline and outlined specific inclusion criteria for enrollment. Blinding of subjects or therapists could not be confirmed in any of the included studies. Only 1 study reported blinding of the outcome assessors. Four of the 5 studies included an adequate follow-up. Intention to treat analysis was carried out in 4 of the 5 included trials. All studies reported between-group comparisons and point estimates with variability measures for at least 1 key outcome were reported in 2 studies. Based on the PEDro scoring, 4 of the 5 included studies were considered high quality and 1 was considered fair quality based on the fulfillment of a random allocation, concealed assignment, blinding of outcome assessors, adequate follow-up, intention to treat analysis, between-group comparisons, and point estimates and variability.

Quality assessment based on PEDro scale of clinical trials included in the meta-analysis.

3.3. Patients

In total, 652 patients were represented across the 5 studies (329 controls and 323 interventions) and 5 countries (Australia, China, Canada, Turkey, and Brazil). They represented patients with cardiac disease awaiting or undergoing mainly coronary artery bypass graft (CABG) surgery, with only 1 study including a fraction undergoing valve replacement surgery, Bentall's procedure, or a combination procedure. [ 14 ] Patients represented largely males in their early 60s, which is consistent with the predominant demographics of heart disease patients undergoing similar procedures in the general population. [ 15 ] While there are many scoring systems to classify patient acuity in the ICU, the Acute Physiologic Assessment and Chronic Health Evaluation (APACHE) II score is among the more common. The scale ranges from 0 to 71, with score aimed at predicting risk of hospital mortality. In this trial cohort, only 1 study provided an APACHE II score of admitted patients. In this study, the mean score was 17.2 for controls and 16.3 for patients in the intervention group. The range coincides with scores reported for vascular surgery patients admitted to the ICU and is associated with a 22% mortality rate. [ 16 ] For the 4 trials which did not report APACHE II scores, 2 provided ejection fraction (EF) at admission, which was taken in this review as a surrogate of risk of mortality at admission. Normal EFs range between 55% and 70% and abnormal scores have been correlated with increased in-hospital mortality. [ 17 , 18 ] EFs reported ranged between <40 and 62%, and, while <40% falls below the “normal” RF rate, this value was used as a threshold for inclusion and did not represent a true average. [ 19 ] Two trials provided no assessment of stability or mortality risk upon admission; however, Patman et al excluded patients with post-operative systolic blood pressure <100 or >180 mm Hg, mean arterial pressure <60 or >110 mm Hg, arrhythmias, or subcostal catheter blood loss >100 mL/hour to control for cardiovascular stability. Overall, no statistically significant differences were reported between control and intervention groups at baseline in either of the included trials. Patient demographics are listed in Table ​ Table3 3 .

Demographic characteristics of patients included in meta-analysis.

3.4. Interventions

Details of the therapies received are outlined in Table ​ Table4. 4 . Three studies initiated early mobilization therapy post-operatively, 1 trial initiated intervention pre-operatively, and 1 study reported peri-operative intervention. The pre-operative intervention was administered twice per week for 8 weeks prior to surgery. While the protocol was not detailed, the intervention was supervised, individualized, and multi-dimensional – with an adherence rate of 87.5%. [ 19 ] In the peri-operative intervention trial, the experimental groups received twice daily (30-minutes sessions) supervised inspiratory muscle training 5 days prior to and 5 days after surgical procedure in addition to usual care (daily, post-operative progressive mobilization and active exercises of the upper and lower limbs and chest physiotherapy). [ 20 ] In one post-operative intervention trial, experimental treatment began during the intubation phase and while physiotherapy was not standardized, techniques included positioning, manual hyperinflation, endotracheal suctioning, thoracic expansion exercises, and upper limb exercises. [ 14 ] In that study, post-extubation care included incentive spirometry and continued (non-standardized) physiotherapy management for all subjects. In another post-surgical intervention trial, early mobilization therapy was initiated on post-operative day 1 until discharge. Experimental treatment in this study included daily supervised progressive exercises ranging from Range of Motion active-assistive movements to stair climbing. [ 21 ] Usual care in that study included daily supervised deep-breathing exercises beginning on post-operative day 1. In the last included trial, post-operative mobilization therapy was supervised twice daily. While precise post-operative intervention start date was not specified, intervention recordings were available for at least 19 sessions. The intervention in this study consisted of a 6-step sequence (including supination, sitting up exercises, standing and walking alongside the bed) that was performed progressively, until the patient signaled tiredness or other termination criteria were met. While intervention was personalized to each patient, completion rates for each step and session were available. During the first intervention session, 100% of participants completed step 1 but only 7.5% completed step 2 and 0% completed the subsequent steps. By the 19th intervention session, 100% of participants were able to complete all 6 intervention steps. [ 22 ]

Description of intervention and control groups of included studies.

3.5. Comparator treatments

The control group in the pre-operative intervention trial included patients followed by their primary care physicians, cardiologists, or surgeons during the surgery waiting period only (usual care). Usual care (administered to all groups) also included educational intervention at baseline and 1 week prior to surgery, at least 1 nurse/physician phone call during the waiting period, and invitation to join cardiac rehabilitation programs post-operatively. [ 19 ] Usual care in the peri-operative intervention trial (administered to all groups) consisted of once daily progressive mobilization and active exercises of the upper and lower limbs, as well as chest physiotherapy commencing on the first post-operative day until the fifth post-operative day. [ 20 ] One post-operative intervention trial was placed specifically during the intubation phase. In this study, the control group was restricted from any physiotherapy or respiratory therapy until the post-extubation, wherein all patients (usual care) included non-standardized physiotherapy management and incentive spirometry. [ 14 ] In the post-operative intervention study by Mendes et al, usual care included no prescribed or supervised inpatient early mobilization, though verbal encouragement for early mobilization was provided. Usual care in this study did included daily supervised deep breathing and coughing exercises beginning from post-operative day 1 for both groups. [ 21 ] In the final post-operative intervention study, patients in the control group received the identical 6-step rehabilitation program; however, the intervention was not supervised by clinical staff and was prescribed only after patients had left the ICU. [ 22 ]

3.6. Effect on interventions: hospital length of stay

All of the 5 included trials reported hospital length of stay for control and experimental groups. The assessment of hospital length of stay represented 308 patients randomized to the experimental condition and 306 randomized controls. Three studies demonstrated a beneficial effect of early physiotherapy (pooled mean difference −1.63; 95% CI: −3.96 to 0.71, Fig. ​ Fig.2a); 2 a); however, the overall effect was not significant ( P  = .17). Of the 3 studies reporting a beneficial effect of intervention, the Dong et al study demonstrated a more dramatic effect (7 times greater than the nearest study). For this reason, a sensitivity analysis was performed excluding Dong et al. In the sensitivity analysis the pooled mean difference was −0.21; 95% CI: −0.75 to 0.34 (Fig. ​ (Fig.2b) 2 b) and the overall effect remained non-significant ( P  = .46).

a. Forest plot for length of hospital stay of 5 trials. b. Forest plot of length of hospital stay of 4 trials.

3.7. Effect on interventions: ICU length of stay

All of the 5 included trials reported ICU length of stay for control and experimental groups. The assessment of hospital length of stay represented 308 patients randomized to the experimental condition and 306 randomized controls. Three studies demonstrated a beneficial effect of early physiotherapy (pooled mean difference −0.98; 95% CI: −2.01 to 0.04, Fig. ​ Fig.3a); 3 a); however, the overall effect was not significant ( P  = .06). Of the 3 studies reporting a beneficial effect of intervention, the Dong et al study once again demonstrated a severely amplified effect (66 times greater than the nearest study). For this reason, a second analysis was performed excluding Dong et al. In the secondary analysis the pooled mean difference was 0.09; 95% CI: −0.12 to 0.29 (Fig. ​ (Fig.3b), 3 b), actually favoring the control condition; however, the overall effect remained non-significant ( P  = .41).

a. Forest plot of length of ICU stay of 5 trials. b. Forest plot of length of ICU stay of 4 trials.

3.8. Qualitative outcomes

The limited number of studies precludes some more commonly reported outcomes and restricts our evaluation to a qualitative nature. Savci et al reported functional changes evaluated by 6 minute walk test (6MWT), specifically changes in meters walked before and after intervention. [ 20 ] Arthur et al reported functional outcomes through the evaluation of the Medical Outcomes Study Short Form 36 (SF-36) physical summary score. [ 19 ] Additionally, the resting heart rate was assessed as physiological outcome by Mendes et al. [ 21 ]

3.9. Adverse events

Only 2 studies reported the adverse effects outcome, which was defined as hospital mortality (reported as percentage of study participants). Dong et al [ 22 ] reported a 2% decrease in-hospital mortality and Mendes et al [ 21 ] reported a 4.2% decrease in-hospital mortality (specifically due to surgical death), though neither of these decreases were not statistically significant.

4. Discussion

4.1. key findings.

Prolonged hospitalization of patients with cardiac disease increases can put patients at increased risk of developing ICU-acquired weakness and in-hospital mortality. Moreover, shortening the length of hospitalization, specifically, can decrease risk of post-operative complications and reduce medical costs. Thus, various early mobilization interventions have been tested in the ICU in the hopes of improving patient outcomes, though a consensus on the effect of such therapies in critically ill patients remains convoluted by a host of population and methodological-level variation. In this systematic review and meta-analysis, early mobilization therapy was evaluated specifically in cardiac patients undergoing non-emergency procedures in a critical care unit. Individually, 3 of 5 randomized trials demonstrated that intervention favored experimentally treated patients compared to controls. In 1 study in particular, the benefits of ICU intervention were dramatically beneficial relative to the other included studies. However, there was no significant reduction in hospital or ICU length of stay overall. In order to verify the influence of low quality studies on the meta-analysis findings, sensitivity analyses were performed for hospital length of stay and ICU length of stay. The study reported by Dong et al [ 22 ] was defined as a low quality according to the PEDro scale (2 reviewers gave a score of 5/10). Therefore, sensitivity analyses required performing the meta-analysis twice: the first time including all studies and a second time excluding the Dong et al study. [ 22 ] Overall results and conclusions were not affected by the decisions made during the review of literature process. Thus, the results of the review can be regarded with a high degree of certainty.

4.2. Relationship to other studies

Several studies have systematically evaluated the effect of early mobilization across critically ill patients. For example, a meta-analysis of early mobilization in pneumonia patients in the ICU found a reduction of mean length of stay (hospitalization) by 1.1 days though this study did not exclusively evaluate randomized controlled trials. [ 23 ] Moreover, in a recent study of monitored daily ambulation in patients undergoing major surgery, higher step counts on post-operative day 1 were associated with reduced probability of prolonged hospital length of stay. [ 24 ] On the other hand, a randomized controlled trial of critically ill patients found no change in ICU or hospital LOS after bedside cycling intervention. Similarly, a study of 104 mechanically ventilated patients found that early exercise and progressive mobilization found no changes in hospital/ICU LOS [ 25 ] and a recent review of early mobilization in critically ill patients similarly concluded that while intervention improved functional status, muscle strength, mechanical ventilation, and quality of life, it did not reduce length of stay or ICU-AW. [ 26 ]

Some evidence of the effectiveness of early mobilization intervention is available in cardiac populations; however, the majority tend to be focused on high-acuity patients such as those admitted to the ICU for myocardial infarction. In fact, a systematic review of more severe acuity respiratory/cardiac failure patients found that out of 9 studies (none were randomized controlled trials), conclusions were focused on the safety of the intervention rather than efficacy of the intervention. [ 27 ]

To the best of our knowledge, early mobilization has only been systematically reviewed in cardiac surgery patients previously by Santos et al, whose meta-analysis attempt was stifled by intervention variability. [ 28 ] This review provided crucial preliminary evaluation of the hemodynamically stable cardiac surgery population targeted in the present review and meta-analysis. Of the 9 included randomized controlled trials, Santos et al found that 3 trials reported significant reductions in hospital length of stay and 1 study in ICU length of stay. The trials included in that evaluation were different from the present study in that they included 4 trials which focused on variations of early mobilization “dose” (i.e., intensity, frequency, duration) rather than strict non-intervention or delayed intervention comparators. The advantage of focusing on a physiologically stable critical care population is that variabilities in intervention initiation are not a major factor, allowing a relatively more standardized prescription of early mobilization. Unfortunately, like Santos et al, the present review encountered lack of clarity in the total duration of intervention which was not apparent in 2 trials, [ 14 , 21 ] mainly due to ambiguity in patients’ post-operative ability to withstand physiotherapy or discharge date. Moreover, adherence was only explicitly addressed in 3 of the 5 trials. [ 14 , 19 , 22 ] Additional limitations included that precise mobilization protocols (including session duration and exercise details) were not available for all included trials and that, though best efforts were taken to streamline the control groups, the fact is that usual care largely includes at least some degree of physiotherapy management or encouragement for independent mobilization which has not been quantified or accounted for in the body of literature.

This meta-analysis included interventions initiated up to 8 weeks pre-operatively and as late as post-operative day 1. While mean duration/frequencies could not be derived for all studies, mobilization sessions ranged between 1.84 and 20 sessions. Of the 2 studies which did specify frequency and duration of intervention (both totaling ∼20 sessions total), the mean estimated total intervention time was slightly over 600 minutes. [ 20 , 22 ] One advantage of the stringent inclusion/exclusion criteria of this review was that though physiotherapy management or early mobilization was not expressly prohibited, no patients assigned to the control group received supervised or prescribed mobilization intervention during the intervention period, reducing the likelihood of comparator group dilution of mean differences.

4.3. Clinical implications of results

Estimated cost savings associated with early mobilization in the ICU are inherently dependent on presumed reductions in hospital length of stay. Therefore, resource and labor burdens of early mobilization implementation in the ICU may not always translate to cost savings across all ICU populations, as the results of this study suggest. Additionally, while deemed predominantly safe, early mobilization in cardiac surgery patients has been linked to some adverse events, including significant hemodynamic alterations (including blood lactate and central venous saturation) which should be carefully monitored in the ICU. [ 29 ] Admittedly, major barriers to safe implementation of early mobilization in the ICU have been reported by physical therapists as insufficient staffing and adequate training. [ 30 ] Combined with the findings from a study of 246 cardiac surgery patients undergoing low (once daily) and high-frequency (twice daily) post-operative exercise rehabilitation, which found no differences in the mean hospitalization length of the 2 groups (average 7 day stay), [ 31 ] the case for post-surgical cardiac patients may be such that the effects of frequent or high intensity early mobilization protocols may not offset resource constraints or safety concerns. It should be noted however that much evidence has continued to point to short-term benefits such as functional improvements and reductions in all-cause mortality in cardiac patients. [ 32 ] At this time, non-standardized protocols for early mobilization, individualized nature of intervention initiation and duration, as well as combined evaluation of diverse critical care populations make it difficult to interpret and extrapolate findings from larger studies. This systematic review and meta-analysis focused on a subset of patients with similar acuity and undergoing very similar surgical conditions as a first step toward eliminating some of the aforementioned confounders. Similarly, broad and common clinical outcomes were selected for meta-analysis, though length of stays may reflect variations in post-surgical complications, functionality, and a wealth of outcomes not covered herein.

5. Conclusions

We found that hospitalization length (ICU and overall) was not significantly impacted by early mobilization therapy. Future studies of this patient population are required to determine additional patient outcomes such as functional capacity, quality of life, long-term survival, etc. Additionally, hospitals should consider means to balance the safety and adequacy of early mobilization intervention with the uniformity required for large-scale evaluation.

Author contributions

BC, GX, and WL designed the study. BC, XY, and WL drafted the protocol and manuscript. DD, XX, XZ, and DL performed the searches and screened the potential studies, extracted the data, assessed the risk of bias, and finished the data synthesis. YL arbitrated any disagreements during the review. All review authors critically reviewed, revised, and approved the subsequent and final version of the manuscript.

Conceptualization: Bin Chen, Wanqing Lin, Guanli Xie.

Methodology: Guanli Xie, Yuan Lin, Xiaofang You, Xuemin Xie, Danyu Dong, Xinyi Zheng, Dong Li.

Software: Lianghua Chen, Zhichen Lin.

Supervision: Bin Chen, Yuan Lin.

Visualization: Bin Chen.

Writing – original draft: Bin Chen, Xiaofang You.

Writing – review & editing: Bin Chen, Xiaofang You, Wanqing Lin.

Abbreviations: CI = confidence interval, CINAHL = Cumulative Index of Nursing and Allied Health Literature, EMBASE = Excerpta Medica database, GRADE = Grading of Recommendations Assessment, Development, and Evaluation, ICU = intensive care unit, ICU-AW = intensive care unit-acquired weakness, PRISMA-P = Preferred Reporting Items for Systematic Reviews and Meta-analyses Protocols, PEDro = Physiotherapy Evidence Database, RCTs = randomized controlled trials, RR = relative risk, SMD = standardized mean difference, WMD = weighted mean difference.

How to cite this article: Chen B, Xie G, Lin Y, Chen L, Lin Z, You X, Xie X, Dong D, Zheng X, Li D, Lin W. A systematic review and meta-analysis of the effects of early mobilization therapy in patients after cardiac surgery. Medicine . 2021;100:15(e25314).

BC and GX contributed equally.

This study was sponsored by Natural Science Foundation of Fujian Province (No. 2019J01497).

The authors have no conflicts of interest to disclose.

The datasets generated during and/or analyzed during the current study are publicly available.

∗ Wildcard operator.

∗∗ Clinical trials filter was applied.

CAD = coronary artery disease, CABG = coronary artery bypass graft.

CABG = coronary artery bypass graft, PO = post operative day, ROM = range of motion.

∗ Protocol not specified.

• Introduction
• Other Important, Ungraded ERAS Elements
• Conclusions
• Article Information

eAppendix. ERAS Glossary of Abbreviations

• JAMA Network Articles of the Year 2019 JAMA Medical News & Perspectives December 3, 2019 This Medical News article discusses the top-viewed Original Investigations and Special Communications published across the JAMA Network over 12 months. Jennifer Abbasi
• The Enhanced Recovery After Surgery in Cardiac Surgery Revolution JAMA Surgery Invited Commentary August 1, 2019 Olle Ljungqvist, MD, PhD

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Engelman DT , Ben Ali W , Williams JB, et al. Guidelines for Perioperative Care in Cardiac Surgery : Enhanced Recovery After Surgery Society Recommendations . JAMA Surg. 2019;154(8):755–766. doi:10.1001/jamasurg.2019.1153

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Guidelines for Perioperative Care in Cardiac Surgery : Enhanced Recovery After Surgery Society Recommendations

• 1 Heart and Vascular Program, Baystate Medical Center, Springfield, Massachusetts
• 2 Montreal Heart Institute, Montreal, Canada
• 3 WakeMed Health and Hospitals, Raleigh, North Carolina
• 4 Centennial Heart & Vascular Center, Nashville, Tennessee
• 5 St Boniface Hospital, University of Manitoba, Winnipeg, Manitoba, Canada
• 6 Cleveland Clinic, Cleveland, Ohio
• 7 MemorialCare Heart and Vascular Institute, Los Angeles, California
• 8 Franciscan Health Heart Center, Indianapolis, Indiana
• 9 Duke University School of Medicine, Durham, North Carolina
• 10 Atrium Health, Department of Cardiovascular and Thoracic Surgery, North Carolina
• 11 St Georges University of London, London, United Kingdom
• 12 Centre Hospitalier Universitaire Vaudois Cardiac Surgery Centre, Lausanne, Switzerland
• 13 University of Calgary, Calgary, Alberta, Canada
• 14 Department of Cardiac Surgery, St Charles Medical Center, Bend, Oregon
• 15 Now with Department of Surgery, Max Rady College of Medicine, University of Manitoba, Winnipeg, Canada
• 16 Department of Surgery, Baystate Medical Center, Springfield, Massachusetts
• Invited Commentary The Enhanced Recovery After Surgery in Cardiac Surgery Revolution Olle Ljungqvist, MD, PhD JAMA Surgery
• Medical News & Perspectives JAMA Network Articles of the Year 2019 Jennifer Abbasi JAMA

Enhanced Recovery After Surgery (ERAS) evidence-based protocols for perioperative care can lead to improvements in clinical outcomes and cost savings. This article aims to present consensus recommendations for the optimal perioperative management of patients undergoing cardiac surgery. A review of meta-analyses, randomized clinical trials, large nonrandomized studies, and reviews was conducted for each protocol element. The quality of the evidence was graded and used to form consensus recommendations for each topic. Development of these recommendations was endorsed by the Enhanced Recovery After Surgery Society.

Enhanced Recovery After Surgery (ERAS) is a multimodal, transdisciplinary care improvement initiative to promote recovery of patients undergoing surgery throughout their entire perioperative journey. 1 These programs aim to reduce complications and promote an earlier return to normal activities. 2 , 3 The ERAS protocols have been associated with a reduction in overall complications and length of stay of up to 50% compared with conventional perioperative patient management in populations having noncardiac surgery. 4 - 6 Evidence-based ERAS protocols have been published across multiple surgical specialties. 1 In early studies, the ERAS approach showed promise in cardiac surgery (CS); however, evidence-based protocols have yet to emerge. 7

To address the need for evidence-based ERAS protocols, we formed a registered nonprofit organization (ERAS Cardiac Society) to use an evidence-driven process to develop recommendations for pathways to optimize patient care in CS contexts through collaborative discovery, analysis, expert consensus, and best practices. The ERAS Cardiac Society has a formal collaborative agreement with the ERAS Society. This article reports the first expert-consensus review of evidence-based CS ERAS practices.

We followed the 2011 Institute of Medicine Standards for Developing Trustworthy Clinical Practice Guidelines , using a standardized algorithm that included experts, key questions, subject champions, systematic literature reviews, selection and appraisal of evidence quality, and development of clear consensus recommendations. 8 We minimized repetition of existing guidelines and consensus statements and focused on specific information in the framework of ERAS protocols.

As sanctioned by the ERAS Society, we began with a public organizational meeting in 2017 where broad topics of ERAS in CS were discussed, and we solicited public comment regarding appropriate approaches and protocols. A multidisciplinary group of 16 cardiac surgeons, anesthesiologists, and intensivists were identified who demonstrated expertise and experience with ERAS. The group agreed on 22 potential interventions, divided into preoperative, intraoperative, and postoperative phases of recovery.

After selecting topics and assigning group leaders, literature searches were conducted according to Preferred Reporting Items for Systematic Reviews and Meta-Analyses (PRISMA) guidelines ( Figure ), and this included reviews, guideline documents, and studies that were conducted on humans since 2000, published in English, and retrievable from PubMed, Excerpta Medica (Embase), Cochrane, the Agency for Healthcare Research and Quality, and other selected databases relevant to this consensus. 9 Medical Subject Heading terms were used, as were accompanying entry terms for the patient group, interventions, and outcomes. Two independent reviewers (W.B.A. and 1 nonauthor) screened the abstracts considered for topics. Prospective randomized clinical trials, meta-analyses, and well-designed, nonrandomized studies were given preference. When multiple publications had sample overlap, the most recent report was selected. Controversies were discussed and resolved via in-person meetings, conference calls, and discussions. A minimum of 75% agreement on class and level was required for consensus. 10 Consistent with the Institute of Medicine guidelines, panel members with relevant conflicts of interest (COI) were identified and recused from voting on associated recommendations. The structure of the recommendations was modeled after prior published ERAS guidelines. 11 We used the Society of Thoracic Surgeons/American Association for Thoracic Surgery 2017 updated document “Classification of Recommendations and Level of Evidence,” and American College of Cardiology/American Heart Association clinical practice guidelines to grade the consensus class (strength) of recommendation and level (quality) of evidence. 10 , 12 ( Box ; eAppendix in the Supplement ).

Class of Recommendation and Levels of Evidence a

Class (strength) of recommendation.

I (strong): benefit many times greater than risk

IIa (moderate): benefit much greater than risk

IIb (weak): benefit greater than risk

III: no benefit (moderate): benefit equal to risk

III: harm (strong): risk greater than benefit

Level (Quality) of Evidence

High-quality evidence from more than 1 randomized clinical trial

Meta-analysis of high-quality randomized clinical trials

One or more randomized clinical trials corroborated by registry studies

Moderate-quality evidence from 1 or more randomized clinical trial

Meta-analysis of moderate-quality randomized clinical trials

Moderate-quality evidence from 1 or more well-designed, well-executed nonrandomized studies or observational studies

Randomized or nonrandomized observational or registry studies with limitations of design or execution

Consensus of expert opinion based on clinical experience

a Adapted from Jacobs AK, Anderson JL, Halperin JL. The evolution and future of ACC/AHA clinical practice guidelines: a 30-year journey: a report of the American College of Cardiology/American Heart Association Task Force 1099 on Practice Guidelines. J Am Coll Cardiol . 2014;64:1373-84. 13 (Reprinted with permission from Elsevier.)

Resulting consensus statements are summarized in Table 1 . They are organized into preoperative, intraoperative, and postoperative strategies.

Optimal preoperative glycemic control, defined by a hemoglobin A 1c level less than 6.5%, has been associated with significant decreases in deep sternal wound infection, ischemic events, and other complications. 13 , 14 Evidence-based guidelines based on poor-quality meta-analyses recommend screening all patients for diabetes preoperatively and intervening to improve glycemic control to achieve a hemoglobin A 1c level less than 7% in patients for whom this is relevant. 15 Despite this recommendation, approximately 25% of patients undergoing CS have hemoglobin A 1c levels greater than 7%, and 10% have undiagnosed diabetes, indicating a failure to apply current evidence-based recommendations for preoperative diabetes management. 16 A recent retrospective review demonstrated that preadmission glycemic control, as assessed by hemoglobin A 1c , is associated with decreased long-term survival. 17 It is unclear whether preoperative interventions in patients undergoing CS will result in improved outcomes. Quiz Ref ID Based on this moderate-quality evidence, we recommend preoperative measurement of hemoglobin A 1c to assist with risk stratification (class IIa, level C-LD) .

Low preoperative serum albumin in patients undergoing CS is associated with an increased risk of morbidity and mortality postoperatively (independent of body mass index). 18 Hypoalbuminemia is a prognosticator of preoperative risk, correlating with increased length of time on a ventilator, acute kidney injury (AKI), infection, longer length of stay, and mortality. 19 - 21 Low-quality meta-analyses support measuring preoperative albumin to prognosticate postoperative CS complications. 21 Based on the moderate quality of evidence, it can be useful to assess preoperative albumin before CS to assist with risk stratification (class IIa, level C-LD).

For patients who are malnourished, oral nutritional supplementation has the greatest effect if started 7 to 10 days preoperatively and has been associated with a reduction in the prevalence of infectious complications in colorectal patients. 22 In patients undergoing CS who had a serum albumin level less than 3.0 g/dL (to convert to g/L, multiply by 10.0), supplementation with 7 to 10 days’ worth of intensive nutrition therapy may improve outcomes. 23 - 26 Currently, however, no adequately powered trials of nutritional therapy initiated early in patients undergoing CS who are considered high risk are available. 27 In addition, this may not be feasible in urgent or emergency settings. Further studies are needed to determine when to delay surgery to correct nutritional deficits. Based on these data, we note that correction of nutritional deficiency is recommended when feasible (class IIa, level C-LD).

Most CS programs mandate that a patient ingest nothing by mouth after midnight for surgery the following day, or at the very least, fast for 6 to 8 hours from the intake of a solid meal before elective cardiac surgery. 28 Several randomized clinical trials have demonstrated, however, that nonalcoholic clear fluids can be safely given up to 2 hours before the induction of anesthesia, and a light meal can be given up to 6 hours before elective procedures requiring general anesthesia. 28 - 30 Encouraging clear liquids until 2 to 4 hours preoperatively is an important component of all ERAS protocols outside of CS. 31 However, no large studies have been performed in populations undergoing CS. The supporting evidence is extrapolated from populations having noncardiac surgery. A small study in patients undergoing CS demonstrated that an oral carbohydrate drink consumed 2 hours preoperatively was safe, and no incidents of aspiration occurred. 32 Aspiration pneumonitis has not been reported, although this potential remains in patients undergoing CS who have delayed gastric emptying owing to diabetes mellitus, and transesophageal echocardiography may also increase aspiration risk. Based on the data available on CS, clear liquids may be continued up to 2 to 4 hours before general anesthesia (class IIb, level C-LD).

A carbohydrate drink (a 12-ounce clear beverage or a 24-g complex carbohydrate beverage) 2 hours preoperatively reduces insulin resistance and tissue glycosylation, improves postoperative glucose control, and enhances return of gut function. 31 In a 2003 Cochrane review 30 of patients undergoing CS, carbohydrate loading reduced postoperative insulin resistance and hospital length of stay. In a large randomized clinical trial 29 , 30 in patients undergoing CS, preoperative carbohydrate administration was found to be safe and improved cardiac function immediately after cardiopulmonary bypass. However, it did not affect postoperative insulin resistance. 33 , 34 Given the current minimal supportive data in patients undergoing CS, carbohydrate loading is given a weak recommendation at this time (class IIb, level C-LD).

Patient education and counseling prior to surgery can be completed in person, through printed material, or through novel online or application-based approaches. These efforts include explanations of procedures and goals that may help reduce perioperative fear, fatigue, and discomfort and enhance recovery and early discharge. Data are emerging that software applications can engage patients, promote compliance, and capture patient-reported outcome measures. 35 They are designed to increase preventive care and encourage patients to perform physical exercise. These platforms have the potential to increase patient knowledge, decrease anxiety, improve health outcomes, and reduce variation in care. 36 , 37 Pilot studies in CS have demonstrated the effectiveness of e-health platforms without any evidence of harm. Thus, it is recommended that these efforts be undertaken 37 (class IIa, level C-LD).

Prehabilitation enables patients to withstand the stress of surgery by augmenting functional capacity. 38 - 40 Preoperative exercise decreases sympathetic overreactivity, improves insulin sensitivity, and increases the ratio of lean body mass to body fat. 41 - 43 It also improves physical and psychological readiness for surgery, reduces postoperative complications and the length of stay, and improves the transition from the hospital to the community. 38 , 39 A cardiac prehabilitation program should include education, nutritional optimization, exercise training, social support, and anxiety reduction, although current existing evidence is limited. 41 - 44 Three non-CS studies 45 - 47 have successfully demonstrated the benefits of 3 to 4 weeks of prehabilitation in the context of ERAS. Prehabilitation interventions prior to CS must be further examined to advance this area of research. The small number of studies and the diversity of validation tools used limits the strength of the recommendation. In addition, this may not be feasible in urgent and emergency settings (class IIa, level B-NR).

Screening for hazardous alcohol use and cigarette smoking should be performed preoperatively. 48 Tobacco smoking and hazardous alcohol consumption are risk factors for postoperative complications and present another opportunity for preoperative interventions. They are associated with respiratory, wound, bleeding, metabolic, and infectious complications. 23 , 49 - 51 Smoking cessation and alcohol abstinence for 1 month are associated with improved postoperative outcomes after surgery. 51 - 53 Only a small number of studies are available, and further CS-specific studies are needed. However, given the low risk of this intervention, patients should be questioned regarding smoking and hazardous alcohol consumption using validated screening tools, and consumption should be stopped 4 weeks before elective surgery. 54 However, this may not be feasible in urgent or emergency settings (class I, level C-LD).

To help reduce surgical site infections, CS programs should include a care bundle that includes topical intranasal therapies, depilation protocols, and appropriate timing and stewardship of perioperative prophylactic antibiotics, combined with smoking cessation, adequate glycemic control, and promotion of postoperative normothermia during recovery. Moderate-quality meta-analysis have concluded that care bundles of 3 to 5 evidence-based interventions can reduce surgical site infections. 55 , 56 This topic has been reviewed extensively with class of recommendation and level of evidence in an expert consensus review by Lazar et al. 57

Evidence supports topical intranasal therapies to eradicate staphylococcal colonization in patients undergoing CS. 57 , 58 From 18% to 30% of all patients undergoing surgery are carriers of Staphylococcus aureus , and they have 3 times the risk of S. aureus surgical site infections and bacteremia. 59 It is recommended that topical therapy be applied universally. 60 - 62 Two studies validate the reduction of such infections in patients receiving mupirocin. 58 , 63 Level IA data exists suggesting that weight-based cephalosporins should be administered fewer than 60 minutes before the skin incision and continued for 48 hours after completion of CS. When the surgery is more than 4 hours, antibiotics require redosing. 64 , 65 Clarity on the preferability of continuous vs intermittent dosing of cefazolin requires further data. 66 A meta-analysis of skin preparation and depilation protocols indicates that clipping is preferred to shaving. 67 Clipping using electric clippers should occur close to the time of surgery. 68 A preoperative shower with chlorhexidine has only been demonstrated to reduce bacterial counts in the wound and is not associated with significant levels of efficacy. 57 Postoperative measures including sterile dressing removal within 48 hours and daily incision washing with chlorhexidine are potentially beneficial. 69 , 70

In summary, we recommend the implementation of a care bundle to include topical intranasal therapies to eradicate staphylococcal colonization, weight-based cephalosporin infusion fewer than 60 minutes before skin incision, with redosing for cases longer than 4 hours, skin preparation, and depilation protocols with dressing changes every 48 hours to reduce surgical site infections (class I, level B-R). The bundle of recommendations to reduce surgical site infections is summarized in Table 2 with the classification of recommendations and level of evidence per Lazar et al. 57

Moderate-quality prospective studies have demonstrated that when rewarming on cardiopulmonary bypass (CPB), hyperthermia (core temperature >37.9°C) is associated with cognitive deficits, infection, and renal dysfunction. 71 - 73 Any postoperative hyperthermia within 24 hours after coronary artery bypass grafting has been associated with cognitive dysfunction at 4 to 6 weeks. 71 Rewarming on CPB to normothermia should be combined with continuous surface warming. 74 Thus, we recommend avoiding hyperthermia while rewarming on cardiopulmonary bypass (class III, level B-R).

Most cardiac surgeons use wire cerclage for sternotomy closure because of the perceived low rate of sternal wound complications and low cost of wires. Wire cerclage brings the cut edges of bone back together by wrapping a wire or band around or through the 2 portions of bone, then tightening the wire or band to pull the 2 parts together. This achieves approximation and compression but does not eliminate side-by-side movement, and thus rigid fixation is not achieved with wire cerclage. 75

In 2 multicenter randomized clinical trials, sternotomy closure with rigid plate fixation resulted in significantly better sternal healing, fewer sternal complications, and no additional cost compared with wire cerclage at 6 months after surgery. 75 , 76 Patient-reported outcome measures demonstrated significantly less pain, better upper-extremity function, and improved quality-of-life scores, with no difference in total 90-day cost. 76 Limitations of these studies include a sample size designed to test the primary end point of improved sternal healing but not the secondary end points of pain and function; in addition, the studies were limited by unblinded radiologists. Additional research 77 - 79 demonstrated decreased mediastinitis, painful sternal nonunion relief after median sternotomy, and superior bony healing when compared with wire cerclage. Based on these studies, the consensus concluded that rigid sternal fixation has benefits in patients undergoing sternotomy and should be especially considered in individuals at high risk, such as those with a high body mass index, previous chest wall radiation, severe chronic obstructive pulmonary disorder, or steroid use. Rigid sternal fixation can be useful to improve or accelerate sternal healing and reduce mediastinal wound complications (class IIa, level B-R).

Bleeding is a common occurrence after CS and can adversely affect outcomes. 80 , 81 Publications on patient blood management are typically focused on reducing red blood cell transfusions through identification and treatment of preoperative anemia, delineation of safe transfusion thresholds, intraoperative blood scavenging, monitoring of the coagulation system, and data-driven algorithms for appropriate transfusion practices. This has been an area of focus in previously published, large, comprehensive, multidisciplinary, multisociety clinical practice guidelines. 82 , 83 The inclusion of all aspects of patient blood management are beyond the scope of these recommendations, although we encourage the incorporation of these existing guidelines within a local ERAS framework. This includes education, audit, and continuous practitioner feedback. Owing to the near-universal accessibility, low-risk profile, cost-effectiveness, and ease of implementation, we did evaluate antifibrinolytic use with tranexamic acid or epsilon aminocaproic acid. In a large randomized clinical trial of patients undergoing coronary revascularization, total blood products transfused, and major hemorrhage or tamponade requiring reoperation were reduced using tranexamic acid. 84 Higher dosages, however, appear to be associated with seizures. 85 , 86 A maximum total dose of 100 mg/kg is recommended. 87 Quiz Ref ID Based on this evidence, tranexamic acid or epsilon aminocaproic acid is recommended during on-pump cardiac surgical procedures (class I, level A) .

Interventions to improve glycemic control are known to improve outcomes. Multiple randomized clinical trials 88 - 91 with diverse patient cohorts support intensive perioperative glucose control. Preoperative carbohydrate loading has resulted in reduced glucose levels after abdominal surgery and CS. 92 , 93 Epidural analgesia during CS has been shown to reduce hyperglycemia incidence. 94 After CS, hyperglycemia morbidity is multifactorial and attributed to glucose toxicity, increased oxidative stress, prothrombotic effects, and inflammation. 14 , 15 , 89 , 91 , 95 Perioperative glycemic control is recommended based on randomized data 96 not specific to populations undergoing CS and high-quality observational studies (class I, level B-R).

Treatment of hyperglycemia (glucose >160-180 mg/dL [to convert to mmol/L, multiply by 0.0555]) with an insulin infusion for the patient undergoing CS may be associated with improved perioperative glycemic control. Postoperative hypoglycemia should be avoided, especially in patients with a tight blood glucose target range (ie, 80-110 mg/dL). 95 , 97 , 98 Randomized clinical trials support insulin infusion protocols to treat hyperglycemia perioperatively; however, more high-quality, CS-specific studies are needed (class IIa, level B-NR).

Until recently, parenteral opioids were the mainstay of postoperative pain management after CS. Opioids are associated with multiple adverse effects, including sedation, respiratory depression, nausea, vomiting, and ileus. 99 There is growing evidence that multimodal opioid-sparing approaches can adequately address pain through the additive or synergistic effects of different types of analgesics, permitting lower opioid doses in the population receiving CS. 100

Nonsteroidal anti-inflammatory drugs are associated with renal dysfunction after CS. 101 Selective COX-2 inhibition is associated with a significant risk of thromboembolic events after CS. 102 The safest nonopioid analgesic may be acetaminophen. 103 Intravenous acetaminophen may be better absorbed until gut function has recovered postoperatively. 104 Per a medium-quality meta-analysis, when added to opioids, acetaminophen produces superior analgesia, an opioid-sparing effect, and independent antiemetic actions. 105 Acetaminophen dosing is 1 g every 8 hours. Combination acetaminophen preparations with opioids should be discontinued.

Tramadol has dual opioid and nonopioid effects but with a high delirium risk. 106 Tramadol produces a 25% decrease in morphine consumption, decreased pain scores, and improved patient comfort postoperatively. 107 Pregabalin also decreases opioid consumption and is used in postoperative multimodal analgesia. 108 Pregabalin given 1 hour before surgery and for 2 postoperative days improves pain scores compared with placebo. 109 A 600-mg gabapentin dose, 2 hours before CS, lowers pain scores, opioid requirements, and postoperative nausea and vomiting. 110

Dexmedetomidine, an intravenous α-2 agonist, reduces opioid requirements. 111 A medium-quality meta-analysis of dexmedetomidine infusion reduced all-cause mortality at 30 days with a lower incidence of postoperative delirium and shorter intubation times. 112 , 113 Dexmedetomidine may reduce AKI after CS. 114 Ketamine has potential uses in CS owing to its favorable hemodynamic profile, minimal respiratory depression, analgesic properties, and reduced delirium incidence; further studies are needed in the CS setting. 115

Patients should receive preoperative counseling to establish appropriate expectations of perioperative analgesia targets. Pain assessments must be made in the intubated patient to ensure the lowest effective opioid dose. The Critical Care Pain Observation Tool, Behavioral Pain Scale, and Bispectral Index monitoring may have a role in this setting. 116 - 119 Although no single pathway exists for multimodal opioid-sparing pain management, there is sufficient evidence to recommend that CS programs use acetaminophen, Tramadol, dexmedetomidine, and pregabalin (or gabapentin) based on formulary availability (class I, level B-NR).

Delirium is an acute confusional state characterized by fluctuating mental status, inattention, and either disorganized thinking or altered level of consciousness that occurs in approximately 50% of patients after CS. 120 - 125 Delirium is associated with reduced in-hospital and long-term survival, freedom from hospital readmission, and cognitive and functional recovery. 126 Early delirium detection is essential to determine the underlying cause (ie, pain, hypoxemia, low cardiac output, and sepsis) and initiate appropriate treatment. 127 A systematic delirium screening tool such as the Confusion Assessment Method for the Intensive Care Unit or the Intensive Care Unit Delirium Screening Checklist should be used. 128 , 129 The perioperative team should consider routine delirium monitoring at least once per nursing shift. 121

Owing to the complexity of delirium pathogenesis, it is unlikely that a single intervention or pharmacologic agent will reduce the incidence of delirium after CS. 127 Nonpharmacologic strategies are a first-line component of management. 130 , 131 There is no evidence that prophylactic antipsychotic use (eg, haloperidol) reduces delirium. 132 , 133 Quiz Ref ID Based on moderate-quality, nonrandomized studies in patients receiving noncardiac surgery, delirium screening is recommended at least once per nursing shift to identify patients at risk and facilitate implementation of prevention and treatment protocols (class I, level B-NR) .

Postoperative hypothermia is the failure to return to or maintain normothermia (>36°C) 2 to 5 hours after an intensive care unit (ICU) admission associated with CS. 134 Hypothermia is associated with increased bleeding, infection, a prolonged hospital stay, and death. Large registry observational studies suggest if hypothermia is of short duration, outcomes can be improved. 135 , 136 Based on this evidence, we recommend prevention of hypothermia by using forced-air warming blankets, raising the ambient room temperature, and warming irrigation and intravenous fluids to avoid hypothermia in the early postoperative period 71 , 137 - 139 (class 1, level B-NR).

Immediately after CS, most patients have some degree of bleeding. 81 If left unevacuated, retained blood can cause tamponade or hemothorax. Thus, a pericardial drain is always necessary after CS to evacuate shed mediastinal blood. 80 Drains used to evacuate shed mediastinal blood are prone to clogging with clotted blood in up to 36% of patients. 140 , 141 When these tubes clog, shed mediastinal blood can pool around the heart or lungs, necessitating reinterventions for tamponade or hemothorax. 142 - 144 Retained shed mediastinal blood hemolyzes and promotes an oxidative inflammatory process that may further cause pleural and pericardial effusions and trigger postoperative atrial fibrillation. 143 , 145

Chest tube manipulation strategies that are commonly used in an attempt to maintain tube patency after CS are of questionable efficacy and safety. One example is chest-tube stripping or milking, in which the practitioner strips the tubes toward the drainage canister to break up visible clots or create short periods of high negative pressure to remove clots. In meta-analyses of randomized clinical trials, chest-tube stripping has been shown to be ineffective and potentially harmful. 146 , 147 Another technique used to maintain patency is to break the sterile field to access the inside of chest tubes and use a smaller tube to suction the clot out. This technique may be dangerous, because it can increase infection risk and potentially damage internal structures. 148

To address the unmet need to prevent chest-tube clogging, active chest-tube clearance methods can be used to prevent occlusion without breaking the sterile field. This has been demonstrated to reduce the subsequent need for interventions to treat retained blood compared with conventional chest tube drainage in 5 nonrandomized clinical trials of CS. 149 - 153 Active chest-tube clearance has also been shown to reduce postoperative atrial fibrillation, suggesting that retained blood may be a trigger for this common problem. 145

While there are no standard criteria for the timing of mediastinal drain removal, evidence suggests that they can be safely removed as soon as the drainage becomes macroscopically serous. 154 Quiz Ref ID Based on these clinical trials, maintenance of chest tube patency without breaking the sterile field is recommended to prevent retained blood complications (class I, level B-NR). Stripping or breaking the sterile field of chest tubes to remove clot is not recommended (class IIIA, level B-R) .

Vascular thrombotic events include both deep venous thrombosis and pulmonary embolism and represent potentially preventable complications after CS. Patients remain hypercoagulable after CS, increasing vascular thrombotic event risk. 155 , 156 All patients benefit from mechanical thromboprophylaxis achieved with compression stockings and/or intermittent pneumatic compression during hospitalization or until they are adequately mobile to reduce the incidence of deep-vein thrombosis after surgery even in the absence of pharmacological treatment. 157 - 159 Prophylactic anticoagulation for vascular thrombotic events should be considered on the first postoperative day and daily thereafter. 160 A recent medium-quality meta-analysis suggested that chemical prophylaxis could reduce vascular thrombotic event risk without increasing bleeding or cardiac tamponade. 161 Based on this evidence, pharmacological prophylaxis should be used as soon as satisfactory hemostasis has been achieved (most commonly on postoperative day 1 through discharge) 160 - 162 (class IIa, level C-LD).

Prolonged mechanical ventilation after CS is associated with longer hospitalization, higher morbidity, mortality, and increased costs. 163 Prolonged intubation is associated with both ventilator-associated pneumonia and significant dysphagia. 164 Early extubation, within 6 hours of ICU arrival, can be achieved with time-directed extubation protocols and low-dose opioid anesthesia. This is safe (even in patients at high risk) and associated with decreased ICU time, length of stay, and costs. 165 - 172 A meta-analysis demonstrated that ICU times and length of stay were reduced; however, no difference in morbidity and mortality occurred, likely because of disparate study design and statistical underpowering. 173 Quiz Ref ID Thus, studies have shown early extubation to be safe, but efficacy in reducing complications has not been conclusively demonstrated. Based on this evidence, we recommend strategies to ensure extubation within 6 hours of surgery (class IIa, level B-NR) .

Acute kidney injury (AKI) complicates 22% to 36% of cardiac surgical procedures, doubling total hospital costs. 174 - 176 Strategies to reduce AKI involve assessing which patients are at risk and then implementing therapies to reduce the incidence. Urinary biomarkers (such as tissue inhibitor of metalloproteinases-2 and insulin-like growth factor-binding protein 7) can identify patients as early as 1 hour after CPB who are at increased risk of developing AKI. 177 , 178

In a randomized clinical trial after CS, patients with positive urinary biomarkers who were assigned to an intervention algorithm had reductions in subsequent AKI. 179 , 180 The algorithm included avoiding nephrotoxic agents, discontinuing angiotensin-converting enzyme inhibitors and angiotensin II antagonists for 48 hours, close monitoring of creatinine and urine output, avoiding hyperglycemia and radiocontrast agents, and close monitoring to optimize volume status and hemodynamic parameters. Similar results have been reported in a randomized clinical trial after surgery in a population who received noncardiac surgery. 181

Although many risk scores for AKI after CS have been published, these scoring systems have good discrimination in assessing low-risk groups but relatively poor discrimination in patients at moderate to high risk. 182 This would suggest that all patients undergoing CS may benefit from detection of modifiable early kidney stress to prevent AKI. Based on these studies, biomarkers are recommended for early identification of patients at risk and to guide an intervention strategy to reduce AKI (class IIa, level B-R).

Goal-directed fluid therapy uses monitoring techniques to guide clinicians with administering fluids, vasopressors, and inotropes to avoid hypotension and low cardiac output. 183 While many clinicians do this informally, goal-directed fluid therapy uses a standardized algorithm for all patients to improve outcomes. Quantified goals include blood pressure, cardiac index, systemic venous oxygen saturation, and urine output. Additionally, oxygen consumption, oxygen debt, and lactate levels may augment therapeutic tactics. Goal-directed fluid therapy trials consistently demonstrate reduced complication rates and length of stay in surgery overall and specifically in CS. 184 - 188 Based on this, we recommend goal-directed fluid therapy to reduce postoperative complications (class I, level B-R).

Preoperative anemia is common and associated with poor outcomes in patients undergoing noncardiac surgery. 189 Patients scheduled for CS may have multifactorial causative mechanisms for anemia, including acute or chronic blood loss, vitamin B12, or folate deficiency, and anemia of chronic disease. 190 If time permits, all causes of anemia should be investigated, but data supporting improved outcomes in the literature on CS is weak. Intraoperative anesthetic and perfusion considerations are also important ERAS elements. Impaired renal oxygenation has been demonstrated during CPB and is ameliorated by an increase in CPB flow. 191 This may contribute to postoperative renal dysfunction and suggests that goal-directed perfusion strategies need to be considered. Other anesthetic considerations may include a comprehensive protective lung ventilation strategy. Multiple studies have established that clinicians should use a low tidal volume strategy for mechanical ventilation in CS. 192 Early postoperative enteral feeding and mobilization after surgery are other essential components of ERAS surgical protocols. 1 We recommend that programs tailor these recommendations to achieve these goals working with staff with expertise in nutrition, early cardiac rehabilitation, and physical therapy.

In CS, a fast-track project to improve outcomes was first initiated by bundling perioperative treatments. 193 The ERAS pathway was initiated in the 1990s by a group of academic surgeons to improve perioperative care for patients receiving colorectal care, but it is now practiced in most fields of surgery. 1 , 194 Although ERAS is relatively new to CS, we anticipate that programs can benefit from these recommendations as they develop protocols to decrease unnecessary variation and improve quality, safety, and value for their patients. Cardiac surgery involves a large clinician group working in concert throughout all phases of care. Patient and caregiver education and systemwide engagement (facilitated by specialty champions and nurse coordinators) are necessary to implement best practices. A successful introduction of ERAS protocols is possible, but a broad-based, multidisciplinary approach is imperative for success.

Accepted for Publication: March 16, 2019.

Corresponding Author: Daniel T. Engelman, MD, Heart and Vascular Program, Baystate Medical Center, 759 Chestnut St, Springfield, MA 01199 ( [email protected] ).

Published Online: May 4, 2019. doi:10.1001/jamasurg.2019.1153

Author Contributions : Dr Engelman had full access to all the data in the study and takes responsibility for the integrity of the data and the accuracy of the data analysis.

Concept and design: D. Engelman, Williams, Perrault, Reddy, Arora, Roselli, Gerdisch, Lobdell, Fletcher, Kirsch, Nelson, Gregory, Boyle.

Acquisition, analysis, or interpretation of data: D. Engelman, Ben Ali, Williams, Perrault, Reddy, Arora, Khoynezhad, Levy, Lobdell, Fletcher, Nelson, R. Engelman.

Drafting of the manuscript: D. Engelman, Williams, Perrault, Arora, Khoynezhad, Gerdisch, Levy, Lobdell, Fletcher, R. Engelman, Boyle.

Critical revision of the manuscript for important intellectual content: D. Engelman, Ben Ali, Williams, Perrault, Reddy, Arora, Roselli, Gerdisch, Levy, Lobdell, Fletcher, Kirsch, Nelson, Gregory.

Statistical analysis: Ben Ali.

Administrative, technical, or material support: D. Engelman, Williams, Perrault, Reddy, Levy, Lobdell, R. Engelman, Boyle.

Supervision: D. Engelman, Perrault, Reddy, Fletcher, Nelson.

Conflict of Interest Disclosures: Dr Khoynezhad consults for and receives speaking honoraria from Atricure Inc. Dr Levy reported serving on research and steering committees for Boehringer-Ingelheim, CSL Behring, Octapharma, Instrumentation Labs, and Merck. Dr Perrault is on the scientific advisory board for ClearFlow Inc and a consultant and principal investigator for Somahlution. Dr Gerdisch is a consultant and principal investigator for and receives speaker honoraria from Zimmer Biomet and Cryolife and consults for and receives speaking honoraria from Atricure Inc. Dr Arora has received honoraria from Mallinckrodt Pharmaceuticals and an unrestricted education grant from Pfizer Canada. Dr R. Engelman is a consultant for Cryolife. Dr D. Engelman reported personal fees from Astute Medical, Edwards Lifescience, and Zimmer-Biomet outside the submitted work. Dr Reddy reports personal fees from Astute Medical outside the submitted work. Dr Arora reports grants from Pfizer Canada and honoraria from Mallickrodt Pharmaceuticals. Dr Roselli reports personal fees from Abbott, Edwards, LivaNova, and Cryolife and grants and personal fees from Gore, Medtronic, and TerumoAortic, outside the submitted work. Dr Boyle reports personal fees from ClearFlow Medical during the conduct of the study and is a founder of and has a patent to ClearFlow Medical pending and issued. No other disclosures were reported.

Disclaimer: The authors verify that all information and materials in this article are original, except for the Box, which is reprinted with permission.

Previous Presentation: American Association for Thoracic Surgery 98th Annual Meeting; April 28 and May 1, 2018; San Diego, California.

Additional Contributions : We thank Olle Ljungqvist, MD, PhD, Örebro University, for his support throughout this process and Gudrun Kunst, MD PhD, FRCA, FFICM, King’s College Hospital, and Michael Grant, MD, Johns Hopkins, for their review of the manuscript. They were not compensated.

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Enhanced recovery after cardiac surgery: A literature review

Navas-Blanco, Jose R.; Kantola, Austin; Whitton, Mark; Johnson, Austin; Shakibai, Nasim; Soto, Roy; Muhammad, Sheryar

Department of Anesthesiology, Oakland University William Beaumont School of Medicine, Corewell Health East, Royal Oak, Michigan, USA

Address for correspondence: Dr. Jose R. Navas-Blanco, Department of Anesthesiology, Oakland University William Beaumont School of Medicine, Corewell Health East, Royal Oak, MI, 48073, USA. E-mail: [email protected]

This is an open access journal, and articles are distributed under the terms of the Creative Commons Attribution-NonCommercial-ShareAlike 4.0 License, which allows others to remix, tweak, and build upon the work non-commercially, as long as appropriate credit is given and the new creations are licensed under the identical terms.

Enhanced recovery after cardiac surgery (ERACS) represents a constellation of evidence-based peri-operative methods aimed to reduce the physiological and psychological stress patients experience after cardiac surgery, with the primary objective of providing an expedited recovery to pre-operative functional status. The method involves pre-operative, intra-operative, and post-operative interventions as well as direct patient engagement to be successful. Numerous publications in regard to the benefits of enhanced recovery have been presented, including decreased post-operative complications, shortened length of stay, decreased overall healthcare costs, and higher patient satisfaction. Implementing an ERACS program undeniably requires a culture change, a methodical shift in the approach of these patients that ultimately allows the team to achieve the aforementioned goals; therefore, team-building, planning, and anticipation of obstacles should be expected.

Introduction

The philosophy of the implementation of enhanced recovery after surgery (ERAS) continues to expand in different surgical specialties. This model has also extended to the management of cardiac patients as the surgical techniques continue to evolve, minimally invasive methods continue to proliferate, and the overall healthcare expectations for improved outcomes and faster tracking of these patients increase. [ 1-4 ]

Enhanced recovery after cardiac surgery (ERACS) represents a constellation of evidence-based peri-operative methods aimed to reduce the physiological and psychological stress patients experience after cardiac surgery, with the ultimate the primary objective of providing an expedited recovery to pre-operative functional status. Overall, the method involves pre-operative, intra-operative, and post-operative interventions; a multi-disciplinary team approach; and direct patient cooperation to be successful. Moreover, implementing an ERACS program undeniably requires a culture change and a methodical shift in the approach of these patients that ultimately allows the team to achieve the above-mentioned goal; therefore, team-building, planning, and anticipation of obstacles are expected.

Numerous publications in regard to the benefits of enhanced recovery have been presented, including decreased post-operative complications, shortened length of stay, decreased overall healthcare costs, and higher patient satisfaction. The majority of data from ERAS comes from colorectal surgery patients, although there has been an increase in data for cardiac surgery patients in recent years. The authors present an updated literature review of the current trends in ERACS.

Enhanced Recovery After Cardiac Surgery

ERACS is a multi-modal approach used in peri-operative patient care that promotes early recovery, improving patient satisfaction, and reducing post-operative morbidity and mortality as well as the length of hospital stay. [ 5 ] ERACS methodology builds off of the ‘fast-track’ approach to cardiac surgery, which emphasizes the use of shorter-acting anesthetic agents and minimally invasive procedures to achieve earlier extubation and shorter intensive care unit (ICU) stays. In addition to the latter, ERACS methodologies incorporate additional peri-operative measures that allow for more comprehensive management of patients and positive clinical outcomes, which ultimately aims for the goal of quicker return to baseline pre-operative status. The interventions used in ERACS cover the patients’ entire surgical experience, including the pre-operative, intra-operative, and post-operative periods. [ 6 ]

ERACS versus “fast-track” recovery after cardiac surgery

The concept of “Fast-Track” after cardiac surgery involves intra-op and post-operative methods aimed to early extubation since rapid ventilator weaning has been typically associated with a shorter length of stay (LOS). “Fast-Track” methods in essence involve all the maneuvers that may be applied to bypass the traditional management of cardiac surgery patients in the past, in which extubation was delayed given the “nature of the procedure”. The concept of “fast-tracking” dates back to the 1990s, in which the pressure of cost containment became evident in the United States’ healthcare system. During this period of time, a fast-tracking peri-operative management aimed to facilitate tracheal extubation within 1–6 hours after cardiac surgery. [ 7 ] The problem was to determine which group of patients would fit within these criteria. Multiple risk models were then proposed based on multi-variate analyses to determine which patients and surgical factors would be associated to a higher chance of success in the “fast-tracking” of cardiac surgical patients, but as expected, none of these risk models were flawless as various peri-operative factors play a substantial role in determining the fast-tracking success. [ 8 ]

The concept of “fast-track” in cardiac surgery eventually showed shorter extubation times and ICU LOS but did not show promising data in terms of rehabilitation, hospital LOS, decreased costs, and so forth. Nonetheless, it became clear that just performing interventions in the intra- and post-operative periods were not sufficient. The need for post-surgical improvement marks the beginning of ERACS as a continuation of the original ERAS, which showed promising results in patients recovering from colorectal surgery. [ 8 , 9 ] Following the same idea of ERAS, ERACS applies a similar concept, integrating the patient experience before, during, and after surgery, with the purpose of not just achieving earlier extubation times but also allowing earlier recovery, returning to baseline function and rehabilitation.

Level of evidence for ERACS interventions

“ERAS Cardiac” represents a comprehensive multi-disciplinary group, where most recent consensus was published in April 2018. The group selected several interventions included in the phases of the patient’s path through recovery, and following the “Classification of Recommendations and Level of Evidence” published by the American College of Cardiology and the American Heart Association as a tool to determine strength of recommendation, the group presented an evidence-based expert consensus statement. [ 10 ] A full statement of these recommendations can be found in www.erascardiac.org. A summary of the “Class of Recommendation” and “Level of Evidence” is presented in Table 1 .

Pre-operative Interventions

Pre-habilitation (class of recommendation iia, level of evidence b-nr).

Pre-habilitation programs consisting of cardio-respiratory and muscular training reduce post-operative complications and positively impact patients’ length of hospital stay. Patients who train pre-operatively for a period of at least 4 weeks have seen reductions in post-operative pulmonary complications such as severe pneumopathy and atelectasis as well as a decreased length of hospital stay. [ 11 ] Exercise represents an intervention that increases functional capacity, improves health status, decreases sympathetic over-reactivity, and improves insulin sensitivity and may be associated to an overall improved psychological readiness for surgery. A comprehensive pre-habilitation program should also be joined with nutrition optimization (N), exercise training (E), and anxiety reduction (W for worry; such intervention is referred as a ‘NEW’ approach). The main disadvantage of pre-habilitation is time; therefore, it becomes less effective depending on the urgency of the surgery. [ 12 , 13 ]

Carbohydrate loading and avoidance of prolonged fasting (class of recommendation IIb, level of evidence C-LD)

Cardiac surgery can cause metabolic stress which can be exacerbated by pre-operative fasting, resulting in a wide range of post-operative complications. Administration of a carbohydrate drink has been associated with reducing insulin resistance and tissue glycosylation, enhancing post-operative glucose control, returning of gut function, and reducing LOS. Additionally, prolonged pre-operative fasting may contribute to post-operative insulin resistance. Continuation of a clear liquid diet up to 2 to 4 hours before surgery is a key component of non-cardiac ERAS protocols. [ 14-16 ]

Correction of nutritional deficiency and support (class of recommendation IIa, level of evidence C-LD)

It is recommended to assess and treat any underlying nutritional deficiency prior to undergoing cardiac surgery. Albumin is commonly used in pre-operative assessment as an indicator for malnutrition and a predictor of post-operative risk/mortality. Rigorous nutrition supplementation for 5–7 days before the procedure may improve outcomes in patients with a pre-operative serum albumin <3 g/dL. [ 17 ] In regard to pre-operative serum glycosylated hemoglobin (HbA1C), a concentration of <6.5% has been associated to decreased post-operative complications including sternal wound infection and myocardial ischemia. In certain cases, depending on the value of HbA1c, it could be necessary to postpone non-urgent surgery to allow for proper glycemic control. [ 18 , 19 ]

Pre-operative smoking and alcohol cessation (class of recommendation I, level of evidence C-LD)

Smoking exposes patients scheduled for surgery to an increased risk of 20% in-hospital mortality and 40% in major post-operative complications. Cessation should be achieved as soon as possible before cardiac surgery for ideal outcomes. In a retrospective analysis involving a total of 3730 male patients undergoing coronary bypass grafting surgery, Ji et al. reported that the risk of post-operative pulmonary complications in persistent smokers was 2.41 times greater than that in non-smokers. While the benefits of smoking cessation increase with the length of cessation before surgery, they should be reviewed routinely, independent of the timing of the planned operation. Similarly, excessive alcohol intake can lead to pulmonary complications, impaired wound healing, bleeding, and metabolic and infectious complications. [ 20-22 ]

Patient engagement and access to technology (class of recommendation IIa, level of evidence C-LD)

Patient activation and engagement in care is associated with a disposition to obtain preventative care, enroll in physical activities before and after surgery, and more importantly understand the nature of the disease involved and the type of surgery to be performed. Numerous e-health innovations have been developed in the recent years; most of them are self-intuitive and are aimed to assist and increase patient self-engagement and improve surgical care. Such innovations aid in the education of the patients, and from the providers’ perspective, it could also allow for patient-reported outcomes to be captured. On the contrary, less engaged patients are roughly three times as likely to have unmet medical needs and twice as likely to delay medical care. [ 23 , 24 ]

Pre-procedure anemia optimization

Optimization of anemia before cardiac surgery is not included in the algorithm proposed in the ERACS protocol developed in 2018. The development of a pre-operative patient blood management (PBM) program aiming to detect and correct iron-deficiency anemia is recommended to reduce adverse outcomes after cardiac surgery. The three pillars of PBM programs are anemia management, minimizing patient blood loss, and analysis of the appropriateness of blood transfusion. Optimizing pre-operative anemia before surgery is an intervention that can be used to reduce the need for intra- and post-operative blood transfusions and reduce the risk of negative post-operative events. [ 11 , 25 ]

In a review conducted by Williams et al. , including data from 182,599 patients who underwent primary isolated on-pump coronary artery bypass grafting (CABG), pre-operative anemia was associated with complications such as mortality, renal failure, deep sternal wound infection, and prolonged hospital stay. Results showed the lowest frequencies of death or complications observed with pre-operative HCT levels of at least 42%. Iron supplementation and erythropoiesis-stimulating agents have been indicated as treatment options for anemic patients with the recommendation to tailor treatment to patients’ specific diagnoses. [ 25 , 26 ]

Intra-operative Interventions

Anti-fibrinolytics (class of recommendation i, level of evidence a).

Anti-fibrinolytic agents in the form of either tranexamic acid (TXA) or epsilon aminocaproic acid have been shown in large randomized controlled trials to provide a significant reduction in the need for blood transfusions in patients undergoing cardiac surgery. These agents work by inhibiting the lysis of polymerized fibrin, blocking the lysine binding site of plasminogen, causing clot stability. TXA is 6–10 times more potent than its similar aminocaproic acid, and higher doses (>100 mg/kg) may lead to seizures, especially in patients with lower seizure threshold and in patients >50 years of age. It is important to emphasize that concurrent administration of systemic heparin does not affect the activity of either drug. [ 27 , 28 ]

Avoidance of hyperthermia (class of recommendation III, level of evidence B-R)

Hyperthermia (>37.9°C) while rewarming on cardiopulmonary bypass is potentially harmful and should be avoided as cerebral hyperthermia after cardiac surgery is associated with neurologic injury and dysfunction. Additionally, hyperthermia has also been linked to increased rates of mediastinitis and post-operative acute renal failure. [ 29-31 ]

Infection reduction bundle (class of recommendation I, level of evidence B-R)

Surgical site infections can be reduced through implementing a “bundle” of evidence-based best practices. Care bundles have demonstrated decreased sternal wound infections and donor site infections by 4.7% and 1.5%, respectively. The ERACS program emphasizes that in order to obtain the best results, such care bundles should not be implemented individually as synergistic application of these measures leads to better results. [ 32 ]

Care bundles include pre-operative chlorhexidine showers, standardization of surgical field preparation, wound protectors, daily washing of the incision with chlorhexidine, administration of cefazolin or cefuroxime 30–60 minutes prior to skin incision, and to continue antibiotic regime for no longer than 48 hours. [ 33 , 34 ]

Optimization of sternal closure (class of recommendation IIa, level of evidence B-R)

Concerns for inadequate bone healing after surgery due to lack of appropriate sternal stabilization promote that cardiac surgery patients recover under “sternal precautions”, which impairs their overall recovery and mobilization. The ERACS consensus recommends rigid plate fixation of the sternum after cardiac surgery as a measure to improve bone healing and reduce mediastinal wound complications. A randomized controlled trial comparing rigid plate fixation and wire cerclage demonstrated better wound healing in the former group as well as fewer sternal complications, improved reported patient outcomes, and no additional costs at 6 months after surgery. Rigid fixation should be specially considered in high-risk patients including morbidly obese, prior chest wall radiation, severe chronic obstructive pulmonary disease, and chronic steroid use. [ 35 , 36 ]

Post-operative Interventions

Early extubation (class of recommendation iia, level of evidence b-nr).

Prolonged mechanical ventilation after cardiac surgery leads to an increased length of ICU and hospital stays, higher costs, and increased morbidity and mortality rates. Early extubation is safe, effective, and practical as part of a cardiac surgery-enhanced recovery protocol and is the gateway to early mobilization and nutrition and a decreased ICU length of stay. It is important to emphasize that the concept of “fast-track” originates for the mere need of early extubation after cardiac surgery, and as clinical concepts have evolved during the last years, ERACS methods have been added to assure that patients get not only extubated faster but also re-inserted back into their pre-surgery lives as smoothly as possible. The ERACS Cardiac Society and the Society of Thoracic Surgeons recommend strategies to ensure extubation within 6 hours of surgery. [ 37 , 38 ]

The benefits of early extubation include earlier patient mobilization, improved hemodynamics without ventilator risks, return to normal feeding, reduced pneumonia risk, reduced need for ICU stay, and reduced duration and dose of sedatives, thereby decreasing delirium incidence and improving cognitive and cardio-vascular recovery. Several factors play a significant role in predicting the “success” of an early extubation protocol, details of which extend beyond the scope of this article, although some of these include a younger age (mean of 61 years old), a lower body mass index (mean of 26.9 kg/m 2 ), absence of chronic lung disease and diabetes, a minimally invasive surgical approach, pre-operative albumin >4 g/dL, isolated CABG, and elective operational status. Brovman et al. demonstrated in a large multi-center analysis that early extubation after surgery (within 6 hours) was not associated with a higher risk of re-intubation after isolated CABG or isolated aortic valve replacement. [ 37 , 39 ]

Multi-modal analgesia (class of recommendation I, level of evidence B-NR)

Opioids are associated with respiratory depression, nausea, vomiting, undesirable sedation, and post-operative ileus. Multi-modal analgesia consists of an essential component of all ERAS pathways based on the “synergistic” effect of non-opioid analgesics. The line between allowing a non-opioid approach and adequate pain control could be very fine, and optimizing pain control after cardiac surgery hastens return to a “normalization” of quality of life and functionality in these patients. [ 40 ]

Opioid doses should be reduced to a goal of <20 mcg/kg of fentanyl (or equivalent). ERACS protocols emphasize the importance of minimizing the use of benzodiazepines and supplementing pain control with other opioid sparing approaches including but not limited to non-steroidal anti-inflammatory drugs when feasible and indicated (i.e., ketorolac, ibuprofen), acetaminophen (either orally pre-operatively or intravenously after surgery), peri-operative gabapentin, dexamethasone, and local anesthetics (either locally as lidocaine transdermal patch, or locally infiltrated after the skin is closed). Regional anesthesia in the formal of truncal blocks (i.e., serratus anterior plane blocks, para-sternal intercostal blocks, para-vertebral blocks) is also an important tool that can be entertained in certain cases, depending on the incision and the type of procedure performed. [ 41 ]

Delirium screening (class of recommendation I, level of evidence B-NR)

Delirium has long been recognized as a complication following cardiac surgery. Delirium is noted for its role in delayed extubation times as well as poor surgical outcomes, increased costs, increased morbidity and mortality rates, and its association with reduced cognitive and functional recovery. Overall, post-operative delirium after cardiac surgery is multi-factorial. Certain risks increase the vulnerability of patients to delirium, including frailty, pre-operative depression, and sub-clinical Alzheimer’s dementia. In addition, women tend to be more prone to develop delirium after cardiac surgery. Current reports estimate that about 20% of patients in cardiac surgery experience delirium post-operatively, nearly twice that of elective non-cardiac procedures. An optimal balance of sedation, analgesia, anxiety, and delirium management may result in reduced post-operative pain, decreased anxiety and delirium, enhanced sleep quality, and improved recovery. An optimal balance of sedation, analgesia, anxiety, and delirium management may result in reduced post-operative pain, decreased anxiety and delirium, enhanced sleep quality, and improved recovery. [ 42 , 43 ]

Goal-directed therapy (class of recommendation I, level of evidence B-R)

Goal-directed therapy (GDT) is a system of hemodynamic treatment goals used to aid in the decisions surrounding the administration of fluids, inotropes, and vasopressors to improve the delivery of oxygen to tissues. The “macro” goals of GDT revolve around the maintenance of patient hemodynamics including cardiac index, systemic blood pressure, and systemic venous oxygen saturation. GDT “micro” goals are generally laboratory parameters that represent biochemical processes such as lactate clearance, inflammation, oxygen consumption, and acute kidney injury biomarkers. Implementation of GDT has shown reduced LOS, reduced infection rates, and a lower incidence of low-cardiac-output syndrome. [ 6 , 11 , 39 ]

Chemical thromboprophylaxis (class of recommendation IIa, level of evidence C-LD)

Vascular thrombotic events (VTEs), including deep vein thrombosis (DVT) and pulmonary embolism (PE), are a potentially preventable form of morbidity and mortality for patients recovering from cardiac surgery. A meta-analysis performed by Ho et al. found that chemical thromboprophylaxis could significantly reduce VTE risk without increasing the risk of bleeding or cardiac tamponade. According to the ERACS society, the strength of this recommendation is limited due to the incorporation of low-quality studies. Despite the sparse data, they suggest thromboprophylaxis as soon as hemostasis is achieved, in addition to mechanical measures via intermittent pneumatic compression devices. [ 44 , 45 ]

Peri-operative glycemic control (class of recommendation I, level of evidence B-R)

Peri-operative hyperglycemia is widely recognized as an indicator of poor post-operative surgical outcomes, associated to direct glycemic toxicity, enhanced oxidative stress and inflammation, and promoting a pro-thrombotic state and increased risk for infections. Improving glycemic control reduces wound-healing complications and reduces post-operative morbidity and mortality. A glycated hemoglobin of less than 7% should be achieved, ideally less than 6.5%. A multi-disciplinary discussion should be contemplated in patients undergoing elective cardiac surgery with a glycated hemoglobin >7% in order to out-weigh risks versus benefits. Educating patients about exercise, diet, cessation of smoking, and minimizing alcohol intake is necessary as these impact HbA1c levels.

Consider using intravenous insulin infusions in hyperglycemic patients undergoing urgent or emergency cardiac surgery, especially if glucose remains above 180 mg/dL, as this is the most effective way to tightly maintain glycemic control (class of recommendation IIa, level of evidence B-NR). [ 46 , 47 ]

Avoidance of hypothermia (class of recommendation I, level of evidence B-NR)

Hypothermia in cardiac surgery is rather common as the majority of the procedures imply the use of cardio-pulmonary bypass, which is usually associated with different degrees of hypothermia. Nevertheless, even mild hypothermia may lead to multiple physiologic derangements including but not limited to increased myocardial demand and further risk of ischemia, delayed wound healing, coagulopathy, prolonged emergence and delayed awakening from anesthesia, and prolonged ventilator use and hospital stay. Active measures should be implemented throughout the peri-operative period to preserve the core body temperature around 36°C–37°C, especially in the intra-operative period and soon after ICU arrival. The use of forced-air warming blankets, warmed intravenous fluids, and warming irrigation are some of the measures that can be implemented to preserve the core body temperature in these patients. [ 48 , 49 ]

Avoidance of acute kidney injury and biomarkers for early detection (class of recommendation IIa, level of evidence B-R)

Cardiac surgery-associated acute kidney injury is a major and common complication and is independently associated with worse short- and long-term outcomes. Varying degrees of acute kidney injury after cardiac surgery can be seen in up to 42% of patients, with 1–5% of these patients requiring renal replacement therapy. Early recognition and implementation of preventive maneuvers are the pinnacle of the management of these patients. Urine output is a functional marker with low sensitivity. Serum creatinine does not become significant before 50% of the renal glomerular filtration capacity is limited and therefore is a “late” indicator of renal injury. [ 50 , 51 ]

Serum biomarkers may allow us to accurately identify patients who had a normal glomerular filtration rate at risk for post-operative acute kidney injury before its onset. Two novel serum biomarkers, insulin-like growth factor-binding protein 7 (IGFBP7) and tissue inhibitor of metalloprotease-2 (TIMP-2), have been proposed and currently are under study to determine patients at risk for cardiac surgery-associated acute kidney injury. The goal ultimately is to identify patients “earlier” and implement measures to avoid kidney injury and decrease costs. Interventions to prevent kidney injury include avoidance of peri-operative hypotension, avoidance of nephrotoxic agents, discontinuation of angiotensin-converting enzyme inhibitors, and angiotensin II receptor blockers. [ 51 , 52 ]

Chest tube drain management (class of recommendation I, level of evidence B-R)

Maintenance of chest tube patency is recommended to prevent retaining blood in the mediastinal or pleural spaces. Active tube clearance has been shown to prevent chest tube occlusion, and several studies have demonstrated a direct relationship between tube clearance and reduction of rates of re-operation for bleeding and post-operative atrial fibrillation. However, high chest tube output of retained mediastinal blood may lead to mechanical compression of heart and lungs, resulting in the requirement of further re-interventions. Small volumes of retained mediastinal blood promote an inflammatory process that may lead to peri-cardial effusions and increase the risk of atrial fibrillation. Stripping or “milking” chest tubes have been widely recognized to be time-consuming and ineffective, and breaking the sterile field to remove a clot is not recommended by the ERACS society (class of recommendation III, level of evidence A). [ 53-55 ]

Implementing an ERACS Program

Starting an ERACS program requires an institutional commitment to cultural change, which includes a multi-disciplinary team building with representation of all key stakeholders including but not limited to nursing, anesthesiology, surgery, mid-level providers, and other related associated clinical teams. A center-specific ERACS protocol following the pre-operative, intra-operative, and post-operative considerations explained above is achievable, ensuring all interested parties have an opportunity to provide input, initiate educational activities to disseminate the program within the institution, and finally perform continuous process monitoring, identification of mishaps, evaluation, and improvement. Standardization is a key driver of success of an ERACS protocol to assure that a protocol that has been widely agreed upon gets executed and to minimize out-of-protocol interventions unless the ERACS coordinators agree. [ 56 , 57 ]

The ERACS program represents a comprehensive pathway to manage cardiac patients throughout all the peri-operative phases of care, with the primary goal of returning to baseline functioning, early recovery, minimizing opioid use, and reduction in health care cost. The application of ERACS protocol standardization requires a multi-disciplinary team commitment, culture change, and sustainability in order to assure the success of the program. Site-specific protocols may be implemented in addition to those suggested by the ERACS program in order to tailor the needs of the institution to the population they serve.

Financial support and sponsorship

Support was provided solely from institutional and/or departmental sources.

Conflicts of interest

There are no conflicts of interest.

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Cardiac surgery; clinical protocols; enhanced recovery after surgery; patient-centered care

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