Effect of mechanical bowel preparation with antibiotics and probiotics on postoperative ileus in patients undergoing posterior lumbar spine surgeries: a randomized controlled trial
Article information
Abstract
Study Design
Randomized controlled trial (RCT).
Purpose
This study aimed to determine the impact of mechanical bowel preparation (MBP) before surgery on postoperative ileus (POI) after elective lumbar spine procedures conducted via a posterior approach.
Overview of Literature
Postoperative Ileus occurs in 5%–12% of spine surgeries. The data relating to spine surgeries is sparse. Previous studies have not shown a significant effect of MBP. However, most of these studies have been conducted on patients undergoing spine surgeries through anterior approaches.
Methods
This RCT included 60 patients (30 in control and 30 in intervention) between 18 and 80 years old, scheduled for elective single or double-level lumbar spine surgeries through the posterior approach. Intervention group (MBP) received PEGLEC, tablet Metronidazole 400 mg twice daily (BD), tablet Cefuroxime 500 mg BD, and probiotic (Bacillus clausii) on pre-operation day, whereas the control (non-MBP) had no specific bowel preparation but received only a placebo. Outcome parameters included time to first flatus, bowel sound, and first defecation, which were compared between the two groups.
Results
Demographic data such as age, sex, body mass index, level of surgery, and intraoperative data such as duration of surgery and blood loss were similar without significant differences. The time to first flatus, bowel sounds, and first defecation was not statistically significant, but POI was seen in 6.67% of patients, all belonging to the MBP group. No correlation observed between the duration of the ileus and the intraoperative blood loss and duration of surgery.
Conclusions
Bowel preparation may not be necessary for patients undergoing posterior lumbar spine surgery involving a maximum of two levels.
Introduction
Postoperative ileus (POI) is characterized by the inability to pass flatus and/or the absence of bowel sounds within 48 hours following surgery. “Uncomplicated” ileus may persist for up to 3 days; however, it is classified as “pathologic” paralytic ileus if it exceeds 3 days and requires intervention [1]. POI is a recognized complication of multiple orthopedic surgeries, with an incidence reported from 5%–12% for spinal procedures [2,3]. POI continues to be a significant concern for both patients and surgeons, and it can contribute to extended hospital stays [4,5]. Postoperative gastrointestinal function is influenced by various factors, primarily the surgical stress response, fluid intake, nutrition, and medications, particularly opiates and epidural analgesics. Researchers have utilized various strategies to address this issue. Pharmacological agents include cholinergic agonists (metoclopramide), serotonin agonists (cisapride, octreotide, etc.), and erythromycin [6–8]. Mechanical bowel preparation (MBP) is a strategy that has been thoroughly investigated in abdominopelvic surgeries [9,10]. However, the results from these studies have been equivocal. The utilization of MBP in spinal surgery is an innovative concept and is infrequently documented in the literature [4,11–13]. Although bowel preparation prior to spine surgery is not standard in most regions, a few locations in India routinely implement preoperative preparation for such procedures, as it is recommended in some textbooks [14,15].
This study seeks to determine the impact of preoperative MBP on POI following elective lumbar spinal procedures conducted via a posterior approach.
Materials and Methods
This was a double-blind, randomized, controlled trial conducted in at the departments of Orthopaedics and Neurosurgery of All India Institute of Medical Sciences (AIIMS), Bhubaneswar, India. The study protocol was approved by the Institutional Ethics Committee, All India Institute of Medical Sciences, Bhubaneswar (Ref. number: IEC/AIIMS BBSR/PG Thesis/2022-23/89, Dated:11/09/2023) and was registered in the Clinical Trial Registry of India (CTRI/2023/06/054230). Adult patients aged 18–65 years, scheduled for elective, single or double-level lumbar spine surgery through a posterior approach who consented to participate in the trial were included. Patients undergoing spine surgery by approaches other than a posterior approach (anterior/lateral), cervical or dorsal spine surgery, emergent spine surgery, or those patients with neurological deficits were excluded. Similarly, patients with previous abdominal surgery, suffering from severe constipation (Wexner score >15), a history of bowel obstruction or electrolyte imbalance, or having an allergy to polyethylene glycol and/or antibiotics used in our protocol were excluded.
Randomization, blinding, and intervention
Patients were randomly divided into two groups using a computer-generated sequence. The experimental group (MBP group) received MBP with antibiotics and probiotics as detailed in Table 1. All administered drugs were kept in sealed packets covered with black tape. The control group (non-MBP) was administered a placebo at identical time intervals as the experimental group. The placebo was also sealed in packets covered with black tape. It was similar in appearance to the drugs administered to the experimental group in amount and appearance to ensure blinding of the subjects. The researchers and the patients were blinded to the treatment allocation (sealed envelope method) and intervention. The person administering the drugs was not part of the study.
The operation for all patients was conducted in the prone position under general anesthesia. Following surgery, all patients received local anesthesia of 10 mL of 0.2% injectable ropivacaine at the wound site and standard analgesics in the form of injectable paracetamol, with injectable diclofenac as rescue analgesia. No opioids were administered for postoperative analgesia. Subjects in both groups were mobilized as soon as possible. Chest physiotherapy and core strengthening exercises were also taught to the subjects in both groups. The outcome scores were evaluated as noted below. Patients were discharged on the 5th postoperative day assuming they were ambulatory and the wound was uninfected.
If the ileus persisted for >48 hours, it was deemed pathological, and interventions were sought for such patients.
Outcome variables
The demographic profile of the patients, including age, gender, body mass index, and level of surgery were noted. Intraoperative assessment of the duration of surgery and blood loss were also documented. The clinical assessment for POI in the postoperative period included: (1) Time to first flatus: this refers to the time of passage of first flatus after surgery. The patient was asked about the time of passage of their first flatus. (2) Time to first bowel sound: this refers to the time when the bowel sounds are heard for the first time after the surgery. The abdomen was auscultated using a stethoscope every 6 hours following surgery for bowel sounds. (3) Time to first defecation: this refers to the time of passage of first stool after surgery. (4) Stool consistency and texture: the consistency and texture of the first stool passed following surgery were assessed using the Bristol stool chart [16]. This chart consists of seven types of stool morphology. For the sake of simplicity, types 1 and 2 were classified as “constipated stool,” types 3 and 4 were classified as “ideal stool,” and types 5–7 were classified as “diarrhea.”
Sample size calculation
To detect a difference of 6 hours in time to first flatus between the groups, with a standard deviation of 8 and level of significance of 0.05, the sample size was calculated to be 56 (28 in each group). To compensate for dropouts, an additional 10% of patients were recruited. This resulted in a total sample size of 60 patients (30 in each group). The alpha and beta errors were assumed to be 5% and 20%.
Statistical analysis
The data was entered into a computer-based spreadsheet and analyzed using IBM SPSS ver. 25.0 (IBM Corp., Armonk, NY, USA). The statistical analysis included calculating means and proportions. The Shapiro-Wilk test was used to assess data normality. The chi-square test (Fisher’s exact test where applicable) was used to compare proportions. A t-test was used for normally distributed data, and the Mann-Whitney U test was used for skewed distributions. A p-value <0.05 was considered significant. Graphs were made using Microsoft Excel 2016 (Microsoft Corp., Redmond, WA, USA).
Results
A total of 60 subjects were included in this study, with 30 in each group. The CONSORT (Consolidated Standards of Reporting Trials) flow diagram is depicted in Fig. 1. Table 2 depicts the demographic profile of the groups, which were similar.
CONSORT (Consolidated Standards of Reporting Trials) flow diagram of the patients between the groups. MBP, mechanical bowel preparation.
The mean time to pass first flatus, bowel sounds, and defecation was slightly greater in the MBP group than in the non-MBP group, although none were statistically significant (Table 3). However, 4/60 (6.67%) did not pass flatus until after 48 hours, and all were in the MBP group (Fig. 2). The consistency of the first stool, as per the Bristol stool chart, involved higher types (types 5–7, diarrhea type) in the MBP group, though none had persistent diarrhea. Subgroup analysis on the primary outcome also did not show any significant differences (Table 4).
There was no correlation between the duration of ileus and intraoperative blood loss (Spearman’s rho coefficient=0.035, p=0.854 for the MBP group and Spearman’s rho coefficient=0.243, p=0.187 for the non-MBP group). There was also no correlation between the duration of ileus and the duration of surgery in the control group (Spearman’s rho coefficient=0.077, p=0.679 for the MBP group and Spearman’s rho coefficient=−0.125, p=0.503 for the non-MBP group).
Complications
We encountered some complications during the study. Three patients (10%) in the MBP group complained of headache on the operative day, and 5/30 (16.67%) in MBP group developed hypotension (systolic blood pressure <90 mm Hg or mean arterial pressure <65 mm Hg) on postoperative day 1, which was managed with intravenous fluids and blood products. No patients in either group developed early infection. There was no prolonged hospitalization (beyond 5 days) for patients in either group.
Discussion
This study aimed to analyze the effects of MBP on POI in patients undergoing spine surgery through a posterior approach. The pathophysiology of POI is a complex interplay between inflammatory and neurogenic mediators [17]. Calcitonin gene related peptide and vasoactive-intestinal peptide are neurogenic mediators, while inflammatory mediators like nitric oxide and prostaglandins, released during surgical manipulation of the intestines during open surgery, activate the splanchnic plexus leading to gut hypomotility and POI [17]. Pharmacological agents such as opioids, epidural analgesics, psychological stress, and a preexisting electrolyte imbalance can also compound the situation. Histologically, Wehner et al. [18] found increased macrophage activity in the intestinal muscularis mucosa during POI.
The rationale behind MBP is that it enhances the voiding of intestinal contents. The MBP regimen is more of an institutional protocol and is not standardized. Choi et al. [19] found polyethylene glycol to be better tolerated by patients and therefore the choice for MBP in our patients. Mechanical cleansing of the bowel is traditionally thought to decrease intestinal microflora, but contemporary studies have shown that patients who received MBP actually have more bacteria [20]. Hence, in our study, we added oral antibiotics and probiotics to the MBP. The choice of ciprofloxacin and metronidazole is based on favorable pharmacokinetics, high bioavailability, and excellent tolerance of the drugs [21]. Ciprofloxacin has better tissue diffusion during surgery with a short half-life (3–5 hours) and also reduces the fecal bacterial load. Additionally, it helps reduce the risk of infections distant from the large bowel, such as urinary tract infections. Metronidazole has been historically used for prophylaxis during colonic surgery since the 1980s [22]. The use of probiotics is a recent addition to nutritional aid. Bengmark and Gil [23] found that using lactobacillus preparations in the pre- and postoperative period may help improve gastrointestinal motility and prevent POI. Therefore, we also used a probiotic solution in our study as a part of the MBP.
The passage of flatus is a subjective finding, whereas auscultation of bowel sounds is objective. Some researchers, however, question the reliability of bowel sounds in diagnosing pathology [20]. We found that both the time to passage of flatus as well as the time to initial bowel sounds were slightly greater in the MBP group compared to the non-MBP group, although none reached statistical significance. But the four patients who had POI by definition all belonged to the MBP group. There was also a trend of delay in passage of the first stool following surgery in the MBP group. MBP did improve the water content of the stool, and more patients had higher Bristol scores as expected. This is unlike Davies et al. [24] who did not find any significant reduction in postoperative rates of constipation in patients with a fractured femur neck who had used laxatives for MBP.
In a review of the literature, particularly of laparoscopic surgeries, Perets et al. [25] reported no significant change in the incidence of POI following bowel preparation. Another survey of elective colonic resection by Sasaki et al. [26], also found no difference between the time to first flatus and first defecation between the two groups. Studies relating to gynecological and gastrointestinal surgery have also concluded that there is no beneficial role to MBP [27,28].
Studies related to spinal surgery are sparse. In one study, Jeon et al. [12] evaluated the effect of MBP on patients undergoing anterior lumbar interbody fusion (ALIF). The authors found a tendency for earlier return of bowel movements in patients receiving MBP, but again this was not statistically significant. Overall, the incidence of POI was high in both groups. This may be due to the direct handling of the bowel during retraction. MBP did not improve ancillary outcomes during ALIF, rather patients had more headache, tiredness, thirst, and abdominal discomfort. There were also cases of hypotension on the day of surgery, similar to our study.
Olsen et al. also studied the role of MBP in patients undergoing posterior spinal instrumentation [11]. They divided patients into three groups (one received an enema, one a suppository, and one with no bowel preparation) and measured the time to first defecation. The authors found that patients who received no bowel preparation recovered from constipation faster than patients in the bowel preparation groups. Most patients did not defecate until the fourth postoperative day, and more patients in the bowel preparation group did not defecate until the 5th postoperative day. This study used opiates as part of the postoperative analgesic regimen which could possibly explain the delay as compared to our study.
Abdulmajeed studied the effectiveness of a preoperative MBP protocol for patients with adolescent idiopathic scoliosis [13]. The authors gave bisacodyl (10 mg) on the day prior to surgery and found fewer postoperative abdominal symptoms in that group, with earlier discharge from the hospital (4±0.6 days vs. 5.3±0.8 days).
In another interesting study, Rezvani et al. [29] found that MBP reduced intraoperative bleeding, the volume of transfusion, and operative time as compared to the control group. The authors hypothesized that MBP decreased the intra-abdominal pressure transmitted to the inferior vena cava and ultimately to the epidural venous system. This sequence of events reduced bleeding during the operation.
The present study attempted to solve the enigma regarding the role of MBP in posterior spinal surgery involving 1–2 levels of fusion. We added probiotics and antibiotics to a previously described MBP. However, there are certain limitations. The study’s primary endpoint was passage of first flatus which is a subjectively assessed parameter, and that may be a potential source of bias. This is a single center study with a small sample size. Our patients’ procedures included only 1–2 spinal levels, and POI may be more symptomatic with more levels of fusion. More levels of fusion are associated with greater blood loss and operative time that ultimately affect the duration of hospitalization. Therefore, further studies with a larger sample size and multiple centers may be needed to validate our findings.
Conclusions
The present study found no benefit for MBP on the postoperative gastrointestinal function of major spinal surgery patients. Since bowel preparation had no significant effect on any postoperative outcomes, the results suggest that this practice should not be considered before major lumbar spine surgery involving up to two levels.
Key Points
Bowel preparation does not improve the incidence of postoperative ileus.
Bowel preparation may not considered in patients undergoing lumbar spine surgeries up to two levels.
The duration of surgery does not affect the duration of postoperative ileus.
Notes
Conflict of Interest
No potential conflict of interest relevant to this article was reported.
Acknowledgments
The authors thank the Indian Council of Medical Research for providing a grant for this study. We also acknowledge the R&D department of Unique Biotech Pharma company for providing placebo and probiotics samples free of cost. We would also like to thank the nursing staff and other medical personnel for their active cooperation.
Funding
The study received funding from Indian Council of Medical Research (Grant no.3/2/Dec-2022/PG-Thesis-HRD(25) dated 01/12/2023).
Author Contributions
Conceptualization: MJ, PK, AS. Data curation: TH. Formal analysis: TH, SK. Funds acquisition: TH. Methodology: MJ, GD. Project administration: SKT, CD. Visualization: TH, MJ. Statistics: CD. Writing–original draft: SK, TH. Writing–review and editing: SK, SKT. Final approval of the manuscript: all the authors.
