Compliance to whole bowel irrigation recommendations: a single poison center study

Abstract Introduction: Whole Bowel Irrigation (WBI) is used as a method of gastrointestinal decontamination for poisoned patients and may have low compliance when recommended by poison centers (PC). We set out to determine WBI compliance and analyze trends and possible associations between WBI compliance and clinical outcomes. Methods: We conducted a single-center retrospective chart review of PC data from 1/1/2011 to 12/31/2019 and included cases in which WBI was recommended. We collected demographic data, exposure history, therapies recommended and performed, and clinical outcomes. Compliance rate was calculated. Chi-squared and Mann-Whitney U tests were performed to look for differences in compliance based on case characteristics such as compliance rate by year, compliance based medication ingested and presence of intubation. We also looked for a possible association between WBI compliance and clinical outcome. Results: Four hundred and eighty-three cases met inclusion criteria. Fifty-five percent of patients were male and the median age was 32.5 years. Compliance to WBI recommendations was 58.2%. There was no significant difference in compliance when comparing by age, gender, medication ingested, or year. There was no association between compliance to WBI and clinical outcomes. Conclusions: We calculated a compliance rate of 58% when WBI was recommended. Compliance to WBI does not appear to be associated with changes in clinical outcome.


Introduction
Whole bowel irrigation (WBI) is a method of gastrointestinal decontamination that is performed when a patient has ingested a potentially toxic dose of a xenobiotic.WBI decreases gastrointestinal transit time and is theorized to decrease drug absorption, mitigating subsequent toxicity.It is performed via rapid administration of a large volume of electrolyte-balanced solution to evacuate the drug from the gastrointestinal lumen before significant absorption can occur.Adult dosing ranges from 1.5 to 2.0 L/hr, and pediatric dosing 25 mL/kg/hr.This is typically done for 4 to 6 h, or until rectal effluent is clear [1].WBI may be indicated in multiple clinical scenarios, some of which are detailed in Table 1 [1].Adverse events associated with WBI include abdominal cramps, bloating, nausea, vomiting, and pulmonary aspiration [1,2].
Despite the fact that WBI has been used for decades, the literature supporting its benefit as a form of gastrointestinal decontamination is sparse, some reporting its benefit, and others reporting no benefit or unclear benefit [3].In 2015, the American Academy of Clinical Toxicology (AACT) and the European Association of Poisons Centres and Clinical Toxicologists (EAPCCT) released an update to their 2004 position paper, stating that with respect to indications for WBI, the clinical toxicology community is "unable to establish a clear set of evidence-based indications for the use of WBI because no clinical outcome studies have ever been performed" [2].In addition, correct performance of WBI is labor intensive and necessitates collaboration between poison specialists, clinicians, nursing staff, and pharmacy staff, which may limit its usage.
A recent retrospective review of Australian PC data reports multiple reasons for non-implementation of WBI, which include both patient factors such as "hemodynamic instability" and "repeated vomiting," but also includes healthcare facility factors, such as "doctor's refusal without specifying reasons for refusal." This study also found that of the 257 patients in which WBI was advised, it was carried out in 150 patients, for a compliance rate of 58%.It was unknown why WBI was not implemented in 39% of cases [4].Compliance to other management recommendations made by PCs for the poisoned patient have been studied as well, and range from 22-72% [5][6][7][8][9].Prior studies introduce reasons why recommendations are not followed to completion, but specific reasons for non-implementation or non-completion of recommendations were not investigated.
We set out to determine WBI compliance when recommended by our PC, and to determine if there are associations between compliance to WBI and clinical outcome.

Methods
We conducted a single-center, retrospective chart review of data from 1 January 2011 to 31 December 2019.Records were retrieved from ToxSentry (TS), the data collection software and electronic medical record (EMR) used at our PC.Inclusion criteria were: any call from a healthcare center to our PC of an ingestion, age ≥ 2 years old, with WBI recommended, and was followed to a known outcome, within the dates described above (Figure 1).We did not include cases in which WBI was performed but not recommended, as this was outside the scope of our research question.There were no prespecified exclusion criteria.The primary outcome of our study was to determine the compliance rate of WBI carried out by healthcare providers when recommended by our PC.Secondary outcomes were to determine any associations between compliance to WBI and clinical outcomes, associations between types of ingestions and compliance to WBI, changes in WBI compliance over time, and to compare WBI compliance rate with compliance rate of other recommendations made by PCs previously reported in the literature.This study was approved by the Emory University Institutional Review Board (IRB) and the Grady Memorial Hospital Research Oversight Committee (ROC).
Calls from the general public or from healthcare settings to our PC are usually first handled by specialists in poison information (SPIs), who collect data from the callers, enter it into the TS software, and provide initial therapeutic recommendations.

indications contraindications
Potentially toxic ingestions of sustained-release and modified release drugs airway protective reflexes are absent or expected to become so in a patient who is not intubated ingestion of a toxic amount of a xenobiotic that is not absorbed to activated charcoal when other methods of gi decontamination are not possible or not efficacious gi tract is not intact.There are signs of ileus, obstruction, significant gi hemorrhage, or hemodynamic instability that might compromise gi motility Removal of illicit drug packets from body packers signs of leakage from cocaine packets (indication for surgical removal) Persistent vomiting Figure 1.inclusion criteria for data collection and subsequent data abstraction and review process and analysis.
Cases were limited to patients already in the healthcare setting at the time of PC notification.The decision to recommend WBI was at the discretion of toxicologist(s) on call for the PC, typically a medical toxicology fellow with attending backup.No specific protocol exists at our PC for addressing noncompliance with PC recommendations, however the on-call toxicologist is generally notified when this occurs.
All cases called into the PC that are followed to a known outcome are designated using specific codes of "no effect," "minor effect," "moderate effect, " "major effect, " or "death." These code designations are consistent with the American Association of Poison Control Centers' (AAPCC) evaluation of toxicity severity associated with the xenobiotic ingested.Minor effects are minimally bothersome symptoms, moderate effects are those which may be prolonged, have systemic involvement, and/or require treatment, and major effects typically are life threatening [10][11].
We also collected demographic data, exposure history including the xenobiotic(s) ingested, therapies recommended and performed, and clinical outcomes.Cases coded as "WBI Recommended, Performed" and "WBI Recommended, Not performed" were used to determine the total number of cases that met inclusion criteria and to calculate a compliance rate.If, during manual review of notes, it was determined that WBI was started but discontinued, we determined that the case should meet coding consistent with "WBI recommended, performed" as our primary goal was to determine compliance of healthcare providers to PC recommendations, regardless of if it was performed to completion.
A manual chart review process was performed by trained, nonblinded data abstractors, consisting of toxicology fellows (authors KS, AG, DN, PF, CW) and one toxicology attending physician (JC).The data abstractors reviewed the clinical notes within TS for accuracy and consistency of SPI documentation and coding, and recorded this data using a standardized data extraction form.Each case was assigned to two abstractors who independently reviewed the clinical notes for each case to determine consistency to the coding within TS.If there was a disagreement between the initial two abstractors' review, a third abstractor would independently review the case and make the tie-breaking decision on whether the SPI notes were consistent with the coding.A Cohen's kappa coefficient was calculated to measure inter-rater reliability between the initial two data abstractors.Abstractors also recorded documented barriers faced during the implementation of WBI using a free text field.
The data collected were analyzed to measure the compliance rate of WBI.Categorical variables were described using frequencies and percentages.Continuous variables (e.g.age) were described using medians and interquartile ranges.Age was compared across WBI groups using the Mann-Whitney U test.Comparisons for categorical variables were conducted using the χ 2 test and Fisher's exact test.Variation in compliance rates across years was evaluated using the χ 2 test and a linear trend across years was evaluated using a logistic regression.Due to the number of comparisons, p values were corrected to control the false discovery rate [12].

Results
There were a total of 483 cases that met inclusion criteria.Fifty-five percent of patients were male and median age was 32.5 years (Table 2).Eighty-seven cases (18%) involved patients under the age of 18, and 18 cases (4%) involved patients under the age of 6.There were 281 cases for which WBI was performed when recommended and 202 cases in which WBI was not performed when recommended, which resulted in a WBI compliance rate of 58.2%.With respect to age and gender, patients who received WBI when recommended did not differ from those who did not receive WBI when recommended.Two hundred and thirty-eight cases were coded as single xenobiotic ingestions, and 245 cases coded as multiple xenobiotic ingestions.The WBI compliance rate was similar between single xenobiotic ingestions (59.7%) and multiple drug ingestions (56.7%; p = .58).
The most commonly ingested xenobiotics for which WBI was recommended were: calcium channel blockers, beta blockers, lithium, methamphetamines, benzodiazepines, antidepressants, cocaine, atypical antipsychotics, iron and iron containing products, and bupropion.Compliance as a function of the xenobiotics ingested is detailed in Figure 2. When controlling for false discovery rate, there was no significant difference between compliance rate of WBI performance based on medication ingested.
Clinical outcomes are presented as a function of compliance to WBI recommendations in Table 2.A moderate clinical effect was the most common outcome (N = 179, 37.1%), followed by minor effects (N = 150, 31.1%),no effect (N = 83, 17.2%), major effects (N = 66, 13.7%), and death (N = 5, 1.0%).Clinical effects based off compliance to WBI recommendations are shown in Figure 3. Two hundred and two cases did not receive WBI when recommended.In this cohort, there were 113 cases in which there was a serious clinical effect (composite of moderate effect, major effect, and death), including two deaths.In comparison, two hundred and eighty one cases did receive WBI when recommended.In this cohort, there were 125 cases in which there was a serious clinical effect, including three deaths.There was no association seen between compliance to WBI and severity of outcome (p = .10).
Intubation was recorded as performed in 80/483 cases (16.6%).The WBI compliance rate was not significantly different for cases in which intubation was performed (50%) compared to cases in which intubation was not performed (59.8%; p = 0.13).
WBI compliance rates by year are shown in Figure 4.The compliance rate varied between 50%, recorded in 2011, and 69.2%, recorded in 2018.A χ 2 test determined that the compliance rate did not vary between years (p = .90)and logistic regression determined that there was no linear trend across years (p = .79).
During the manual chart review phase of our study, data abstractors found eight cases without manual entries.These cases were assumed to be coded accurately and were included in the final analysis.Data abstractors also found 32 cases in which the coding and the SPI written notes were inconsistent with the initial code, namely that review of the SPI clinical notes indicated that WBI was never performed.We included these in the final analysis as we had not considered this scenario as a prespecified exclusion criteria.If instead we chose to assume that WBI was not performed in any of these 40 cases, this would lower our primary outcome of WBI compliance to 49.9%.The inter-rater reliability, represented by a Cohen's kappa coefficient, was measured to be 0.78, indicating substantial agreement between the data abstractors.Review of SPI notes included documentation of reasons WBI was not initiated, was interrupted, or was not implemented to completion.Examples included patient vomiting, refusal to drink, error in medication administered, and lack of proper equipment to perform the procedure.

Discussion
In our study WBI was performed in 58.2% of cases when recommended by our PC.Our measured compliance rate falls within the range of compliance rates of other recommendations made by poison centers (22-72%) [4][5][6][7][8][9].While our results for WBI are consistent with compliance rates of other recommendations made, there may be areas in which poison centers can improve on to increase compliance rate to WBI recommendations by hospitals and healthcare providers.One previous PC study compared using telephone recommendations against faxed information sheets and found no change in compliance [8].It is possible that direct consultation between the on-call medical toxicologist and treating physician might provide more context and evidence, increasing compliance with recommendations.This is common practice at our PC with critically ill patients, however we did not collect information on how often it occurred in this study.Further research is needed to see what interventions improve compliance to PC recommendations [4][5][6][7][8][9].
We found no association between compliance to WBI recommendations and clinical outcomes, and also found that over time, compliance to WBI recommendations has not changed.It is notable that 44% of patients who did not receive WBI when recommended, and 51% of those who did, had either no or minor clinical effects.Recommendations for WBI are often made early in the clinical course based upon history alone, and it is quite possible that many reported ingestions never took place.Unfortunately self-reported ingestion history can be quite unreliable [13].Alternately, it is possible that in these cases WBI effectively mitigated toxic effects of the substance(s) ingested.Deguigne et al. also recently conducted a retrospective review of PC data and concluded that WBI appeared to provide a possible clinical benefit in body packers and patients poisoned with massive doses of drugs or non-charcoal-adsorbable toxins, although this analysis was performed with different outcome classifications and utilized different statistical methodologies [4].While it is possible that our data could have revealed a potential benefit for WBI in specific exposures, the current study was not primarily designed to evaluate this hypothesis.
We did not find a statistically significant difference between compliance rate of WBI performance based on medication ingested.However, WBI was performed  70% of the time when recommended for ingestions involving iron and bupropion and only 44% of the time for ingestions involving atypical antipsychotics.This variation in compliance rate may be due to the relatively increased amount of literature describing WBI as a therapeutic, or lack of effective therapy specific to certain xenobiotics.For example, there is a relatively abundant literature showing WBI as a beneficial management option in iron ingestions [14][15][16].With respect to bupropion, toxicity is clinically challenging to manage, as it manifests with delayed onset seizures as well as cardiac conduction abnormalities via gap junction interactions [17].Because of the lack of good antidotal therapy for bupropion toxicity, it is often recommended that aggressive GI decontamination measures, including WBI, are performed to mitigate the delayed toxicity.In addition, compliance to WBI for cases involving iron and bupropion may be relatively higher in comparison to other xenobiotic ingestions as the ingestions of these xenobiotics fall clearly within the indications for WBI.Iron and iron containing substance ingestions fall under the indication of "Ingestion of a toxic amount of a xenobiotic that is not absorbed to activated charcoal when other methods of GI decontamination are not possible or not efficacious," and many bupropion ingestions fall under the indication of "Potentially toxic ingestions of sustained-release and modified release drugs" as this xenobiotic comes in a sustained release and extended release formulation [1][2].These higher compliance rates of bupropion (70%) and iron-containing products (70.6%) were not observed by Deguigne et al. and may be unique to our region's prescribing and ingestion patterns.They reported higher compliance rate in body lithium salts (68.6%), "Other metals" (76.5%), and body packers (70%).Our data-entry system did not have a "body-packer" or "body-stuffer" designation, but ingestions of cocaine and methamphetamine had WBI compliance rates of 65% and 66%, respectively.Together, our data distinguish certain ingestions that are associated with relatively higher than average compliance rates, and future investigations in these ingestions should be performed.
Case reports show that some patients do not tolerate WBI.Cumpston et al. reported two patients who received WBI and experienced associated adverse events, including persistent vomiting and aspiration [18].The incidence of adverse events associated with WBI has been reported to be as high as 10-18% [5,19].Manual chart review of SPI notes within TS revealed scenarios similar to previously reported adverse events.Some examples were documented as "WBI was stopped [secondary to] nausea, " or "patient could not tolerate [secondary to] vomiting."Because of these adverse effects, it may be recommended that a patient have a protected airway before WBI is initiated, and it is debated that nasogastric/orogastric tube placement for WBI may be better tolerated in the intubated patient rather than the awake patient.Manual chart review revealed that in a small number of cases, intubation was performed for the purpose of initiating WBI.We do not recommend intubation for the sole purpose of initiating WBI.Our study showed no statistical difference between compliance rates of WBI between the cohort of patients who were intubated versus those who were not.However, our data does not clearly detail the temporal relationship between intubation and performance of WBI.
Our data describes multiple issues with delays in initiation of WBI, unexpected pauses, and other barriers faced with complete implementation of WBI.While there are patient-centered factors that contribute to the improper performance of WBI, such as self-removal of nasogastric tube, and development of nausea and vomiting, there are also hospital-centered and procedure-centered barriers that contribute to the practicality of proper WBI performance.The data abstractors detailed scenarios in which healthcare facilities administered the incorrect medication (polyethylene glycol without electrolytes, magnesium citrate), did not have the proper materials to administer the medication at the rates required, or continued WBI despite meeting endpoints or developing contraindications to the procedure.Some of these barriers to completion of WBI described within our poison center data have not been previously described in the literature and may offer potential areas of focus for improving compliance rates.The rate of WBI recommendation by our PC varied over time and may represent varying practice patterns of fellows in the program at any given time.Future quality improvement projects to develop and refine a WBI protocol at our PC may increase compliance.

Limitations
Our results are limited in that this was a retrospective study of PC data and relies on the accurate reporting of healthcare information from healthcare facilities as well as accurate and complete charting by the PC.Precise timing of ingestions, symptoms, and therapies is difficult to ascertain based upon PC data and we did not have access to hospital-level charts.Data entry occurred at the physician level at time of exposure, the SPI level at time of PC involvement, and the data abstractors level at the time of our research period, introducing the possibility of transcription error.Literature published describing the bias associated with chart review studies such as ours describes multiple layers of bias researchers face when trying to publish data from chart review [20].Our study attempted to limit this through the use of training, standardized data abstraction templates, and parallel review by multiple abstractors for each chart.In our analysis, we included 8 cases without manual entries, and 32 cases where there was inconsistency between coding and documentation; these cases may have introduced bias into our results.Finally, this single center study may reflect practice patterns specific to our region and may not be generalizable to other regions.

Conclusions
We calculated compliance rate of WBI performance to be 58% when recommended.Compliance to WBI does not appear to be associated with changes in clinical outcome.However, WBI is a complex process, and patient-centered, hospital-centered, and procedure-centered barriers prevent proper initiation, implementation and completion of WBI.Further investigation into these barriers is warranted.

Figure 3 .
Figure 3. clinical Effects By compliance to WBi Recommendations by Pc.
* P value computed from a mann-Whitney u or χ 2 test.† P value following the false discovery rate correction.