The decision to operate on a patient for small bowel adhesion obstruction (SAO) has long presented a management dilemma. The old paradigm of early surgical intervention introduced the adage “never let the sun go down on an intestinal obstruction” [1].
There is now robust evidence that an initial trial of non-surgical management is safe in appropriately selected patients [2-4]. Oral water-soluble contrast agents (ACSA), such as diatrizoate meglumine-diatrizoate sodium (gastrografin), have proven useful in selecting those for whom nonoperative management will fail.
The presence of gastrografin in the colon on serial plain radiographs, known as “gastrografin challenge,” can predict the resolution of a partial intestinal obstruction [5]. The prognostic role of gastrografin often obviates the need for surgery earlier in the hospital course, which may reduce length of stay [5,6], and curb healthcare costs [7].
ACSAs may also have therapeutic value in accelerating the progression of an OAID [6,8], and reducing the need for surgical intervention [9,10], although the evidence in this regard remains equivocal [11-13]. The therapeutic mechanism of gastrografin’s action is thought to be based on its properties as an osmotic compound and wetting agent, which displaces water into the lumen of the intestine and facilitates intestinal motility[14].
Considering the diagnosis and the possible therapeutic action of gastrografin, the authors of this work hypothesized that early administration of gastrografin may provide clinical benefit in patients with OAID.
- As a diagnostic tool , early use of contrast can accelerate clinical decision making, by classifying patients into surgical and non-surgical, at an earlier stage in the hospital course.
- As a therapeutic modality , timely administration of gastrografin may be important in alleviating interstitial edema within a critical window, before complete obstruction or strangulation forms.
The purpose of this study was to evaluate the optimal timing of ACSA administration, comparing its early (≤ 12 hours) and late (> 12 hours) use. The primary outcome was mean length of stay. Secondary outcomes included: operative requirement, mean time to operating room (OR), mean number of complications, complication rate, 1-year recurrence rate, and 1-year mortality rate.
Additionally, bivariate and multivariate logistic regression analyzes were used to evaluate whether the timing of gastrografin administration or any other factor was predictive of 1-year mortality in their cohort.
| Methods |
This work is a retrospective review of records from a database of patients who were diagnosed with OAID by computed tomography (CT), from January 2016 to January 2018, and who were subjected to the gastrografin challenge. Data were collected from two separate hospitals within a single healthcare system. Internal review board approval was obtained.
Only patients who presented with signs and symptoms of abdominal pain and who underwent CT were included. Institutional policy is to avoid the use of contrast on initial CT in patients who may have an obstruction. All patients were then treated with nasogastric decompression and received 60 to 90 cc of gastrografin, as part of their diagnostic evaluation.
Patients who presented with small bowel obstruction due to causes other than adhesions, such as a mass, volvulus, inflammatory bowel disease, or hernia, were not included. Patients with signs of strangulation or perforation, corresponding to grade IV and V obstruction, according to the American Association for the Surgery of Trauma , were not included [15,16]. Patients who had undergone surgery within 6 weeks of presentation, or who had no history of abdominal surgery, were not included.
A receiver operating characteristic (ROC) curve was created to determine the optimal time threshold for gastrografin administration. Based on the ROC curve, a cutoff at 12 hours was selected.
Subsequently, patients were classified into early (≤ 12 h) or late (> 12 h) groups of gastrografin administration after CT diagnosis. The timing of gastrografin administration and time to OS were calculated using the number of hours from the performance of an initial diagnostic CT scan in the emergency room.
Baseline characteristics including age, sex, body mass index (BMI), comorbidities, and surgical history were compared between the 2 groups. The primary outcome was length of stay. Secondary outcomes included: operative requirement, mean time to OS, complications, complication rate, 1-year recurrence rate, and 1-year mortality rate. Surgical and non-surgical patients were compared independently.
A separate analysis was performed to evaluate 1-year survival in the patient population. Patients were classified into the groups ≥ 1 year of survival, and without survival. The timing of gastrografin administration was compared between the 2 groups, along with other factors, including comorbidities, surgical history, complications, and operative requirement.
All variables that were significant in the bivariate analysis were included in a multivariate stepwise logistic regression to determine which variables were independent risk factors for 1-year mortality.
> Statistical methods
An ROC curve was created to determine the optimal threshold timing for gastrografin administration. The curve demonstrated the sensitivity and specificity of the timing of gastrografin administration across the spectrum of test values, in predicting a length of stay ≤ 5 days.
The resulting cut-off point, 12 hours, had optimal sensitivity and specificity, 80% and 57% respectively, for predicting a length of stay ≤ 5 days. A length of stay of 5 days was chosen because it reflects the average length of stay in patients with OAID [1]. This value represents best practices for OAID management. The cut-off at 12 hours was calculated before performing any statistical comparison.
The t and c2 tests were used to compare continuous and categorical variables between each study group. Statistical analyzes were 2-sided, and P < 0.05 was considered statistically significant.
In the survival analysis, variables with a P < 0.05 were included in a multivariate logistic regression to measure the outcome of 1-year mortality. All statistical analyzes were performed with SPSS, version 22 (IBM Corporation, Armonk, NY).
| Results |
In the 134 patients who met the inclusion criteria, the mean age was 66.7 years (standard deviation [SD] 17.68). The mean time for gastrografin administration was 28.0 hours (SD: 29.3). Of all patients, 20.1% required surgical intervention. One-year mortality was 8.2%.
In total, 6 patients died during hospitalization. Acute kidney injury was the most common complication during hospitalization, affecting 11 patients. There was 1 aspiration event, but it was not related to gastrografin use. There were no complications during hospitalization directly related to the administration of gastrografin.
Between the early and late groups there was no statistically significant difference in baseline demographic data, including age, sex, BMI, and surgical history. The late group had a higher incidence of arrhythmia than the early group.
Otherwise, there was no significant difference in any of the baseline comorbidities. In terms of outcomes, the early group had a shorter length of hospital stay (3.2 vs 5.4 days), lower mean number of complications (0.08 vs 0.43), a lower complication rate ( 8.2% vs 27.6%), and a lower 1-year mortality rate (0.0% vs 10.3%) ( P < 0.05).
Regarding the operated patients, there was no statistically significant difference between the early and late groups in baseline demographic data, including age, sex, BMI, and surgical history.
In terms of outcomes, the early group had a shorter duration of preoperative hospital stay (1.8 vs. 3.9 days), and a shorter time to OS (43.7 vs. 94.6 hours). Other outcomes, including overall length of stay, postoperative length of stay, complications, 1-year recurrence, and 1-year mortality, were not significantly different between the groups.
Compared with survivors (≥ 1 year), nonsurvivors had a higher mean age, a longer mean time to gastrografin administration, a higher incidence of congestive heart failure (CHF), a higher mean number of complications and complication rate, higher SO requirement, and longer length of stay ( P < 0.05).
In multivariable logistic regression, after controlling for other factors, CHF, any postoperative complication, and operative requirement, were the best independent predictors of 1-year mortality (R2 = 0.321; P < 0.05).
| Discussion |
OAID is a common cause of emergency department attendance and hospitalization in patients with prior abdominal surgery [17,18]. The management of OAID is associated with significant morbidity and costs to the healthcare system [18,19].
This can be largely explained by the high rate of disease recurrence and the frequent need for emergency surgical interventions [20,21]. A 2016 study found that lysis of peritoneal adhesions was the fifth most cumbersome procedure performed in the US, based on mortality, complications, and healthcare costs [22].
The decision to operate on patients with OAID has long presented a diagnostic dilemma. In their landmark study in 2013, Schraufnagel et al. showed that 4 or more preoperative days were associated with prolonged length of stay and increased mortality, reinforcing a general trend in favor of early surgical intervention [1]. .
This contrasts with level 1 evidence and societal guidelines validating the safety of initial non-operative management in patients without generalized peritonitis or clinical deterioration [2]. In the last decade, a more nuanced approach has been invoked, using ACSA guidance to predict who will fail the non-operative trial [23].
Echoing that sentiment, recent guidelines recommend studies with water-soluble contrast, using the gastrografin challenge, as part of standard OAID management [4]. However, the optimal timing for administration of gastrografin within this approach remains unclear.
Eight randomized controlled trials, from 1996 to 2017, studying the diagnostic and therapeutic role of ACSA in OAID, did not present a consensus on the duration of preoperative management [7-13,24]. Six of these trials administered gastrografin after an unspecified period of nasogastric decompression, presumably depending on practitioner preference. Di Saverio et al., described an intake of gastrografin administered immediately after the diagnosis of OAID [9]. The most recent trial, by Scotte et al., protocolized 100 cc of gastrografin delivered after 2 hours of nasogastric tube decompression [12].
The authors of the present work proposed a cut-off of 12 hours as the optimal time frame for the administration of gastrografin. This cut-off point was determined before the statistical analysis based on retrospective data, so it has limitations. However, they favored using that cutoff because it is based on data. On the other hand, they consider that a 12-hour cutoff fits clinically well into the general paradigm of modern acute care surgery.
This is the first study to show a clinical benefit of early gastrografin challenge, within 12 hours of CT diagnosis, in the management of OAID. In terms of the primary outcome, early administration of gastrografin shortened length of stay by approximately 2 days in nonsurgical patients. Although this did not significantly reduce the overall length of stay in surgical patients, it significantly shortened the preoperative length of stay and time to OS.
In the comparison of early and late use of gastrografin in non-operated patients, length of stay, number of complications, complication rate, and 1-year mortality were significantly lower in the early group.
The authors attribute these gains to limiting the morbidity of prolonged nonoperative management in patients who received early gastrografin.
Several studies have demonstrated faster resolution of symptoms, return of first bowel movement, and initiation of oral feeding, with the use of gastrografin, compared to standard nonsurgical management [6,24]. The authors of the present work suggest that the use of gastrografin could enhance this process.
From a diagnostic standpoint, nonsurgical patients who received early gastrografin were triaged earlier for conservative management, which likely accelerated resumption of enteral nutrition, minimized the morbidity of prolonged nasogastric decompression, and resulted in more discharge. early.
The overall complication rate in nonsurgical patients who received gastrografin late was quite high (27.6%), compared with the early group (8.2%). It is well established that prolonged gastric drainage is associated with physiological disorders, most notably dehydration, electrolyte abnormalities, renal dysfunction, and metabolic alkalosis [4,25,26].
In the study population, the most common complication was acute kidney injury (AKI) (11 cases). More than half of the AKI cases were represented in non-surgical patients who received gastrografin late (6 cases).
The authors suspect that the disproportionate incidence of AKI in this group reflects the known association of prolonged nasogastric tube decompression and dehydration in the setting of an extended hospital stay.
Other complications were also disproportionately present in nonsurgical patients who received gastrografin late, including atrial fibrillation (7 cases), respiratory failure (3 cases), and sepsis (3 cases). Similarly, these complications may reflect the deleterious effects of prolonged hospitalization.
The authors hypothesized that early use of gastrografin did not present similar gains in morbidity and mortality in surgical patients, primarily due to an “equalizing” effect of surgery. Specifically, the results in the surgical patients were due more to complications inherent to the surgery and the postoperative period (which were identical in the early and late groups) than to the morbidity of a prolonged preoperative period.
It should be noted that compared with nonsurgical patients, the overall complication rate and mortality rate were relatively high. Indeed, in the context of surgery-specific complications, the influence of early gastrografin use in the preoperative window was negligible.
Additionally, it is possible that the preoperative delay in the late group was not significant enough to produce a clinical change. Although the preoperative length of stay between the early and late groups was significantly different (early: 1.8 days; late: 3.9 days), surgical patients who received gastrografin late were still operated on in a timely manner, on average within of the 4 days from the presentation.
Multiple studies have shown that extending the length of preoperative hospitalization from 3 to 4 days does not increase overall morbidity and mortality in patients with OAID. Keenan et al., in a review of 9000 patients with OAID, only found a significant increase in 30-day morbidity and length of stay after the 3rd preoperative day and the 4th day, respectively [27].
Similarly, Schraufnagel et al. demonstrated a benefit in mortality and length of stay if the preoperative length of stay was 4 or more days [1]. Assuming that the preoperative delay was not robust enough to affect a difference, it is expected that the results between the early and late groups could be similar in the surgical patients.
In addition to improving diagnostic efficiency, early gastrografin challenge may also confer therapeutic benefits. The pathophysiology of OAID is a progressive process derived from the accumulation of edema of the intestinal wall, in the context of a mechanical obstruction.
Gastrografin contains an ionic component with considerable osmolarity, as well as a wetting agent. The increase in osmolarity promotes a shift of intraluminal fluid across the obstructive site, while the wetting agent facilitates the passage of feces through a narrow lumen [14].
Considering the pathophysiology of OAID, there may be a critical window after which the degree of interstitial edema cannot be overcome by the osmolar gap created by ACSA. By giving gastrografin early, within 12 hours in this study cohort, the authors could have optimized that therapeutic window.
They hypothesized that nonsurgical patients most likely have low-grade obstructions, which are amenable to reversal or accelerated resolution, and who may have uniquely benefited from a therapeutic standpoint.
Despite the proposed benefits of early use of gastrografin, clinicians may be hesitant to implement an early contrast protocol due to concerns about aspiration, especially in patients with many comorbidities.
Notably, of the 148 patients who were reviewed, none of the complications were directly related to gastrografin administration. In review of the literature, specific complications of ACSA, such as aspiration or anaphylaxis, are extremely rare [28]. However, the authors anticipate that in clinical practice there may be a selection bias toward avoiding early use of gastrografin in elderly or ill patients.
As for the present analysis, the only baseline factor significantly different between the early and late groups was a higher incidence of arrhythmia in nonsurgical patients who received late gastrografin. The authors do not believe that this association is substantive enough to represent significant selection bias.
All other baseline factors, including demographics, BMI, smoking history, previous episodes of small bowel obstruction, surgical history, and comorbidities, were not statistically different between the early and late study groups. Generally, they consider that the benefit of early use of gastrografin outweighs the lower risk of aspiration, and should not be a reason to avoid early use of contrast, even in patients with many comorbidities.
In the regression analysis, CHF, having any complication, and surgical requirement, considered simultaneously, were the best independent predictors of 1-year mortality. Multiple risk assessment tools have validated CHF as an independent risk factor for complications and mortality before non-cardiac surgery [29,30]. In their regression analysis, Schraefnagel et al. also reported CHF as an independent predictor of death [1].
As noted previously, operative requirement in patients with OAID has been associated with mortality [31,32]. Similar findings have been found in terms of postoperative complications and mortality [33].
Although the mean time of gastrografin administration was lower in the survivor group, this did not withstand multivariable regression. It is unclear whether early administration of ACSA offers any additional benefit in terms of mortality. The authors suspect that if there is any mortality benefit to early use of gastrografin, it is specific to decreasing prolonged conservative management, especially in nonsurgical patients.
There were several limitations to this study. There are inherent biases in recall of information associated with retrospective studies. Findings were not compared with a control group of patients not receiving ACSA. Furthermore, the duration of symptoms in the patients in the cohort before their hospitalization was not known. Although baseline characteristics, including surgical history and medical comorbidities, were similar between groups, it is unknown whether the duration of symptoms before hospitalization affected the study design and results.
In conclusion , this is the first study that found a benefit with early gastrografin challenge in the management of OAID.
The authors propose a maximum window of 12 hours of non-surgical nasogastric decompression before gastrografin challenge. Protocolizing that measure to a comprehensive intestinal obstruction algorithm will likely decrease length of stay and time to OS, which could have overall effects on the cost of healthcare. Early gastrografin may also improve the morbidity and mortality associated with prolonged nonsurgical management. In the future, more prospective studies are necessary to explore the benefits of early use of gastrografin. |
