Rapid rehabilitation effect on complications, wound infection, anastomotic leak, obstruction, and hospital re-admission for gastrointestinal surgery subjects: A meta-analysis.

We performed a meta-analysis to evaluate the effect of rapid rehabilitation on the curative effect of gastrointestinal surgery subjects. A systematic literature search up to October 2021 was done and 31 studies included 4448 subjects with gastrointestinal surgery at the start of the study: 2242 of them were provided with rapid rehabilitation and 2206 were standard care. They were reporting relationships about the effect of rapid rehabilitation on the curative effect of gastrointestinal surgery subjects. We calculated the odds ratio (OR) with 95% confidence intervals (CIs) to assess the effect of rapid rehabilitation on the curative effect of gastrointestinal surgery subjects using the dichotomous method with a random- or fixed-effect model. Rapid rehabilitation had significantly lower complications (OR, 0.62; 95% CI, 0.54-0.71, P < .001) and wound infection (OR, 0.73; 95% CI, 0.55-0.98, P = .03) compared with standard care in subjects with gastrointestinal surgery. However, rapid rehabilitation had no significant effect on the anastomotic leak (OR, 0.90; 95% CI, 0.66-1.22, P = .49), obstruction (OR, 0.92; 95% CI, -0.64 to 1.31, P = .65), and hospital re-admission (OR, 0.78; 95% CI, 0.57-1.08, P = .13) compared with standard care in subjects with gastrointestinal surgery. Rapid rehabilitation had significantly lower complications and wound infection, and had no significant effect on the anastomotic leak, obstruction, and hospital re-admission compared with standard care in subjects with gastrointestinal surgery. Further studies are required to validate these findings.

BACKGROUND

Rapid rehabilitation protocols have often been studied in the literature. The idea of rapid rehabilitation protocols was first recommended by a Danish surgeon, Kehlet, to decrease stress, complications, and hospital length of stay following gastrointestinal surgery. Rapid rehabilitation protocols were studied primarily in the location of elective gastrointestinal surgery. , They showed, by improving and perioperative care standardisation, the hospital length of stay can be decreased from 8 to 12 days to 2 to 4 days. , For the surgical management of gastrointestinal cancer illness, conservative elective gastrointestinal surgery is related to a high rate of complication (10%‐45%) and a postoperative hospital length of stay (8‐13 days). , A higher percentage of dangerous postoperative complications are related to an extreme response to surgical stress. , C‐reactive protein, interleukin‐6, tumour necrosis factor‐α, and resting energy expenditure might act as markers for the surgical stress response severity. , , To solve this problem, rapid rehabilitation protocols were established. Rapid rehabilitation protocols are established to decrease surgical stress by different surgical and anaesthetic methods to improve recovery. In a prospective study examining the value of an enhanced recovery in elective gastrointestinal surgery, it was shown that a number of the rapid rehabilitation protocols principles, for example, avoidance of prophylactic nasogastric tubes and abdominal drains, use of multimodal analgesia, and early postoperative feeding, can be used effectively in this clinical situation without increasing postoperative illness. The safety of rapid rehabilitation protocols is still conflicting. So, this meta‐analysis aimed to assess the effect of rapid rehabilitation on the curative effect of gastrointestinal surgery subjects.

METHODS

The current study was completed following a reputable protocol that was based on the meta‐analysis of studies in the epidemiology statement.

Study selection

Comprised studies were that with statistical relationship (odds ratio [OR], mean difference [MD], frequency rate ratio, or relative risk, with 95% confidence intervals [CIs]) among the effect of rapid rehabilitation on the curative effect of gastrointestinal surgery subjects.

Only those human studies in any language were selected. Inclusion was not limited by study size or type. Studies excluded were review articles, commentaries, and studies that did not provide a level of association. Figure 1 shows the entire study procedure. The articles were combined into the meta‐analysis when the next inclusion criteria were met:Exclusion criteria were as follows:

FIGURE 1

Schematic illustration of the study method

The study was a randomised control trial, prospective study, or retrospective study.

The target population was subjects with gastrointestinal surgery.

The intervention programme was rapid rehabilitation.

The study comprised comparisons between rapid rehabilitation and standard care.

Studies that did not determine the effect of rapid rehabilitation on the curative effect of gastrointestinal surgery subjects.

Studies with management other than rapid rehabilitation.

Studies that did not focus on the effect of comparative results.

Identification

A protocol of search plans was arranged based on the PICOS principle, and we defined it as follow: P (population): subjects with gastrointestinal surgery; I (intervention/exposure): rapid rehabilitation; C (comparison): rapid rehabilitation and standard care; O (outcome): complications, wound infection, anastomotic leak, obstruction, and hospital re‐admission; and S (study design): no limit. First, we performed a systematic search of Embase, PubMed, Cochrane Library, OVID, and Google scholar till October 2021, by a blend of keywords and related words for rapid rehabilitation, gastrointestinal surgery, standard care, complications, wound infection, anastomotic leak, obstruction, and hospital re‐admission as shown in Table 1. All selected studies were grouped in an EndNote file, duplicates were removed, and the title and abstracts were reviewed to remove studies that did not show any association about the effect of rapid rehabilitation on the outcomes of care for subjects with gastrointestinal surgery. The remaining studies were studied for associated information.

TABLE 1

Search strategy for each database

Database	Search strategy
PubMed	#1 ‘rapid rehabilitation’[MeSH Terms] OR ‘gastrointestinal surgery’[All Fields] OR ‘standard care’[All Fields] #2 ‘complications’[MeSH Terms] OR ‘rapid rehabilitation’[All Fields] OR ‘wound infection’[All Fields] OR ‘anastomotic leak’[All Fields] OR ‘obstruction’[All Fields] OR ‘hospital re‐admission’[All Fields] #3 #1 AND #2
Embase	‘rapid rehabilitation’/exp OR ‘gastrointestinal surgery’/exp OR ‘standard care’/exp #2 ‘complications’/exp OR ‘ICBG’/exp OR ‘wound infection’/exp OR ‘anastomotic leak’/exp OR ‘obstruction’/exp OR ‘hospital re‐admission’/exp #3 #1 AND #2
Cochrane Library	#1 (rapid rehabilitation):ti,ab,kw OR (gastrointestinal surgery):ti,ab,kw OR (standard care):ti,ab,kw (Word variations have been searched) #2 (complications):ti,ab,kw OR (wound infection):ti,ab,kw OR (anastomotic leak):ti,ab,kw or (obstruction):ti,ab,kw or (hospital re‐admission):ti,ab,kw (Word variations have been searched) #3 #1 AND #2

Screening

Data were shortened depending on the following; study‐related and subject‐related properties onto a homogeneous form as follow: the primary author last name, study period, country, publication year, the studies region and type of the population, and design of the study; the total number of subjects, demographic data, and clinical and treatment properties. In addition, the evaluation period is related to measurement, quantitative technique and qualitative technique of assessment, source of information, outcomes' evaluation, and statistical analysis of MD or relative risk, with 95% CI of relationship. If a study fit for inclusion depended on the abovementioned principles, data were extracted separately by two authors. In case of dissimilarity, the corresponding author gives a final choice. When there were different data from one study based on the evaluation of the relationship between the effects of rapid rehabilitation compared with standard care on the outcomes of care for subjects with gastrointestinal surgery, we extracted them separately. The risk of bias in these studies: each study was appraised using two authors who separately evaluated the procedural quality of the nominated studies. The ‘risk of bias tool’ from the RoB 2: A studied Cochrane risk of bias tool for randomised trials was used to measure procedural quality. In terms of the evaluation criteria, each study was valued and consigned to one of the next three risks of bias: low: if all quality standards were met, the study was considered to have a low risk of bias; unclear: if one or more of the quality standards were partly met or unclear, the study was considered to have a moderate risk of bias; or high: if one or more of the standards were not met, or not comprised, the study was considered to have a high risk of bias. Any discrepancies were addressed by reviewing the original article.

Eligibility

The chief result concentrated on the effect of rapid rehabilitation on the curative effect of gastrointestinal surgery subjects. An evaluation of the effect of rapid rehabilitation on the curative effect of gastrointestinal surgery subjects was extracted to make a summary.

Inclusion

Sensitivity analyses were limited only to studies showing the association of the effect of rapid rehabilitation on the curative effect of gastrointestinal surgery subjects. For subgroup and sensitivity analysis, we performed a comparison between rapid rehabilitation and standard care.

Statistical analysis

We computed the odds ratio (OR) and 95% confidence interval (CI) by the dichotomous technique with a fixed‐ or random‐effect model. We calculated the I2 index, and the I2 index was between 0% and 100%. When the I2 index was around 0%, 25%, 50%, and 75%, it refers to no, low, moderate, and high heterogeneity, respectively. If the I2 was >50%, we used the random‐effect model; if it was <50%, we used the fixed‐effect model. We used stratifying the original calculation per result category as defined before the subgroup analysis. A P value for differences among subgroups of <.05 reflected statistically significant. Studies bias was measured quantitatively using the Egger regression test (studies bias is present if P ≥ .05), and qualitatively, by visual examination of funnel plots of the logarithm of odds ratios against their standard errors. The entire P values were two‐tailed. Reviewer manager version 5.3 (The Nordic Cochrane Centre, The Cochrane Collaboration, Copenhagen, Denmark) was used to perform all measurements and graphs.

RESULTS

A total of 1021 distinctive studies were found, of which 31 studies (between 2003 and 2021) satisfied the inclusion criteria and were comprised in the study. , , , , , , , , , , , , , , , , , , , , , , , , , , , , , , The 32 studies included 4448 subjects with gastrointestinal surgery at the start of the study: 2242 of them were provided with rapid rehabilitation and 2206 were standard care. All studies evaluated the effect of rapid rehabilitation on the curative effect of gastrointestinal surgery subjects.

The study size ranged from 25 to 597 subjects with gastrointestinal surgery at the beginning of the study. The information of the 31 studies is shown in Table 2. Twenty‐nine studies reported data stratified to the complications, 19 studies reported data stratified to the wound infection, 19 studies reported data stratified to anastomotic leak, 12 studies reported data stratified to the obstruction, and 16 studies reported data stratified to the hospital re‐admission.

TABLE 2

Characteristics of the selected studies for the meta‐analysis

Study	Country	Total	Rapid rehabilitation	Standard care
Anderson 14	United Kingdom	25	14	11
Basse 15	Denmark	60	30	30
MacKay 16	United Kingdom	80	22	58
Gatt 17	United Kingdom	39	19	20
Khoo 18	United Kingdom	70	35	35
King 19	United Kingdom	60	41	19
Ionescu 20	Romania	96	48	48
Šerclová 21	Czech Republic	103	51	52
Muller 22	Switzerland	151	76	75
Faiz 23	United Kingdom	211	161	50
Hübner 24	Switzerland	67	36	31
Wang 25	China	92	47	45
Vlug 26	Netherlands	400	193	207
van Bree 27	Belgium	72	36	36
Wang 28	China	210	106	104
García‐Botello 29	Spain	119	61	58
Ren 30	China	597	299	298
Yang 31	China	62	32	30
Wang 32	China	78	40	38
Veenhof 33	Netherlands	79	36	43
Wang 34	China	163	81	82
Hu 35	China	82	40	42
Srinivasa 36	New Zealand	74	37	37
Ni 37	China	160	80	80
Lemanu 38	New Zealand	78	40	38
Jia 39	China	233	117	116
Vignali 40	Italy	297	162	135
Maggiori 41	France	263	130	133
Ostermann 42	Switzerland	150	75	75
Nechay 43	Russia	104	50	54
Tesauro 44	Italy	173	47	126
	Total	4448	2242	2206

Rapid rehabilitation had significantly lower complications (OR, 0.62; 95% CI, 0.54‐0.71, P < .001) with low heterogeneity (I2 = 37%), and wound infection (OR, 0.73; 95% CI, 0.55‐0.98, P = .03) with no heterogeneity (I2 = 8%) compared with standard care in subjects with gastrointestinal surgery as shown in Figures 2 and 3.

FIGURE 2

Forest plot of the complications in subjects with gastrointestinal surgery with rapid rehabilitation compared with the standard care

FIGURE 3

Forest plot of the wound infection in subjects with gastrointestinal surgery with rapid rehabilitation compared with the standard care

However, rapid rehabilitation had no significant effect on the anastomotic leak (OR, 0.90; 95% CI, 0.66‐1.22, P = .49) with no heterogeneity (I2 = 0%), obstruction (OR, 0.92; 95% CI, −0.64 to 1.31, P = .65) with no heterogeneity (I2 = 0%), and hospital re‐admission (OR, 0.78; 95% CI, 0.57‐1.08, P = .13) with low heterogeneity (I2 = 26%) compared with standard care in subjects with gastrointestinal surgery as shown in Figures 4, 5, 6.

FIGURE 4

Forest plot of the anastomotic leak in subjects with gastrointestinal surgery with rapid rehabilitation compared with the standard care

FIGURE 5

Forest plot of the obstruction in subjects with gastrointestinal surgery with rapid rehabilitation compared with the standard care

FIGURE 6

Forest plot of the hospital re‐admission in rapid rehabilitation group compared with the standard care group

Studies stratified analysis that adjusted for ethnicity, and age was not completed because no studies stated or adjusted for these influences.

Depending on the visual assessment of the funnel plot as well as on quantitative measurement by the Egger regression test, there was no sign of publication bias (P = .88). Yet, the majority of the included studies were of low procedural quality because of their small sample size. All studies did not have selective reporting bias, and no study had incomplete outcome data and selective reporting.

DISCUSSION

This meta‐analysis study based on 31 studies included 4448 subjects with gastrointestinal surgery at the start of the study: 2242 of them were provided with rapid rehabilitation and 2206 were standard care. , , , , , , , , , , , , , , , , , , , , , , , , , , , , , , Rapid rehabilitation had significantly lower complications and wound infection compared with standard care in subjects with gastrointestinal surgery. However, rapid rehabilitation had no significant effect on the anastomotic leak, obstruction, and hospital re‐admission compared with standard care in subjects with gastrointestinal surgery. Yet, the analysis of results must be done with attention because of the low sample size of most of the selected studies found for the meta‐analysis, 16 out of 31 studies with less than 100 subjects as sample size, recommending the necessity for additional studies to confirm these findings or perhaps to significantly impact confidence in the effect assessment.

The safety of rapid rehabilitation protocols after gastrointestinal surgery has been well discussed internationally. The latest analysis confirmed that male gender, pre‐operative education, counselling, anaesthetics, early postoperative oral nutrition, and care quality were possible complications risk factors after gastrointestinal resection. Also, many studies have shown a high risk of anastomotic leaks in men compared with women because 10.1% of the men needed reoperation for anastomotic leak compared with 3.3% of women. , Pre‐operative education and counselling are vital factors for rapid rehabilitation protocols. It is essential to present the detailed management programme, rapid rehabilitation protocols' different steps, and related procedures, and decrease the psychological pressure to help subjects understand and organise the rapid rehabilitation protocols. Better collaboration of subjects can bring better results of rapid rehabilitation protocols. The solid meal and fluid gastric emptying time are 6 hours and 2 hours, respectively. Reasonable activity after surgery might enhance recovery and decrease complications. The subjects should be stimulated to have a liquid meal 2 hours before the operation in place of fasting. It has been reported that pre‐operative oral carbohydrate is safe and can efficiently decrease complications. , The role of regional anaesthesia or epidural in rapid rehabilitation protocols should be stressed. Postoperative epidural analgesia can avoid stress‐induced neurological, endocrinological, and homeostatic variations or the blocking of the sympathetic nerve‐related surgical stress response, decrease postoperative complications, eg, nausea, vomiting, and enteroparalysis, increase early ambulation, recover intestinal function, and shorten hospital stay after resection of gastrointestinal cancer. , , Early postoperative oral nutrition is a vital part of rapid rehabilitation protocols. Food consumption can encourage gastrointestinal peristalsis, and quick feeding in the first 24 hours after surgery stimulates obstruction recovery. It has been shown that early postoperative oral nutrition reduces catabolism and possibly reduces infectious complications. , Rapid rehabilitation protocols can increase the subjects' rehabilitation after gastrointestinal cancer surgery better than standard care plans, so benefiting surgery, anaesthesia, pain treatment, physical treatment, and social work. The main effort of rapid rehabilitation protocols is the pre‐operative education of subjects to let them understand the entire strategy and the objective of each phase. So, it is essential to obtain collaboration from nurses. The pathophysiological mechanisms in postoperative obstruction are still not completely understood; nevertheless, the latest studies have stressed the importance of the intestinal muscularis inflammation following the handling during surgery. , ,

The mechanisms behind the beneficial influence of rapid rehabilitation protocols are still conflicting. Numerous cytokines, for example, interleukin‐6, tumour necrosis factor‐α, and C‐reactive protein, are included in the response to surgical stress and are consequently useful serum markers for assessing the severity of surgery‐induced stress. , C‐reactive protein is a general acute‐phase protein created by the liver after trauma or inflammation. Serum C‐reactive protein level is closely related to trauma and stress, so quantifying postoperative C‐reactive protein might imitate the degree of the trauma initiated by a surgical process. Interleukin‐6 is created and initiated by monocytes, macrophages, and endothelial cells in surgical trauma and stress. Interleukin‐6 levels are related to the surgical trauma severity. , Surgical trauma results in noticeable metabolic variations and resting energy expenditure. Also, it acts as the marker for surgical stress. , The resting energy expenditure rate of subjects from the rapid rehabilitation protocols group was lower than that in the standard care group, mainly on postoperative days 1 and 3. Post‐surgical complications in subjects who experienced rapid rehabilitation protocols for colorectal illnesses were managed without definite side effects or complications. Compared with standard care plans, rapid rehabilitation protocols greatly decreased complications, and no other side effects were found. Rapid rehabilitation protocols are safe and possible. We believe that rapid rehabilitation protocols are significantly beneficial over other methods for subjects after gastrointestinal cancer surgery.

This meta‐analysis reported the association of the effect of rapid rehabilitation on the curative effect of gastrointestinal surgery subjects. However, other studies are needed to confirm these probable relationships. Also, additional studies are required to provide a clinically meaningful difference in the outcomes. This was suggested also in previous similar meta‐analysis studies, which showed a similar effect of rapid rehabilitation and standard care in subjects with different types of surgery. , , , , , , , , The insignificant results of rapid rehabilitation in the anastomotic leak, obstruction, and hospital re‐admission also need additional study and clarification because no clear reasoning was found to clarify these outcomes. Well‐conducted studies are also required to measure these factors and the blend of different ages and ethnicity; because our meta‐analysis study could not answer whether they are related to the outcomes. Most of the selected studies evaluated were designed and accompanied before 2013, when SPIRIT Statement was started as a protocol to assist in improving the quality of clinical trial protocols. The CONSORT Statement (2010) is a 25‐item checklist and flow diagram for authors to confirm transparent reporting of randomised trials. Using the SPIRIT and CONSORT protocols and checklists when designing and reporting a randomised controlled trial will assist in confirming that all vital elements of the trial are reported. Therefore, reducing the risk of bias eventually will help increase the quality of rapid rehabilitation of randomised controlled trials. , We suggest that well‐designed, high‐quality randomised controlled trials are required to be accomplished about the effect of rapid rehabilitation on gastrointestinal surgery subjects. Health care providers need to confirm completed studies are published to establish and document results related to the effect of rapid rehabilitation on gastrointestinal surgery subjects because published evidence should be used to lead the clinical practice.

In summary, rapid rehabilitation had significantly lower complications and wound infection compared with standard care in subjects with gastrointestinal surgery. However, rapid rehabilitation had no significant effect on the anastomotic leak, obstruction, and hospital re‐admission compared with standard care in subjects with gastrointestinal surgery. Further studies are required to validate these findings.

Limitations

There might be selection bias in this study because numerous studies found were excluded from our meta‐analysis. Yet, the studies excluded did not fulfil the inclusion criteria of the meta‐analysis. Also, we could not answer whether the outcomes were related to age and ethnicity or not. The study was intended to evaluate the association of the effect of rapid rehabilitation on the outcomes of care for subjects with gastrointestinal surgery depending on data from earlier studies, which may originate bias brought by incomplete information. The meta‐analysis was based on only 31 studies: 16 studies were small, ≤100. There was significant heterogeneity between the selected studies, and the risk of introducing possibly significant heterogeneity could occur. Also, the publication bias in favour of the rapid rehabilitation might account for this heterogeneity after the sensitivity analysis. Variables, for example, age, ethnicity, and nutritional condition of subjects, were also the probable bias‐inducing influences. Some unpublished articles and omitted data may cause a bias in the pooled result. Subjects were using different management programmes, doses, and health care organisations. The length of rapid rehabilitation management of the comprised studies was inconsistent.

The comprised studies did not sufficiently assess the hospital costs and quality of life after surgery, which are vital results for subjects experiencing elective colorectal surgery.

CONCLUSIONS

Rapid rehabilitation had significantly lower complications and wound infection compared with standard care in subjects with gastrointestinal surgery. However, rapid rehabilitation had no significant effect on the anastomotic leak, obstruction, and hospital re‐admission compared with standard care in subjects with gastrointestinal surgery. Further studies are required to validate these findings. More studies are essential to confirm these outcomes. Yet, the analysis of results must be done with attention because of the low sample size of most of the selected studies found for the meta‐analysis, recommending the necessity for additional studies to confirm these findings or perhaps to significantly impacts confidence in the effect assessment.