ARTICLE 1593

Caustic Ingestion: A Risk-Based Algorithm

ENDOSCOPY
Joan Tosca, MD, PhD1, Ana Sánchez, MD1, Ana Sanahuja, MD1, Rosana Villagrasa, MD1, Paloma Poyatos, MD1, Pilar Mas, MD, PhD1,
Isabel Pascual, MD, PhD1, Paloma Lluch, MD, PhD1, Belén Herreros, MD, PhD2, Andrés Peña, MD, PhD1, Vicente Sánchiz, MD, PhD1 and
Miguel Mínguez, MD, PhD1

INTRODUCTION: Caustic ingestion management could be improved with a diagnostic approach based on risk factors.
This study aimed to develop an algorithm derived from predictive factors of a poor clinical course, to
evaluate its diagnostic accuracy and resource consumption, and to compare it with 2 other
approaches, a radiological one based on computed tomography and a classical one based on
symptoms and endoscopy.
METHODS: All patients older than 15 years presenting with caustic ingestion in our tertiary care hospital between
1995 and 2021 were prospectively included. Adverse outcome was defined as intensive care unit
admission, emergency surgery, or death. Ingestion characteristics, symptoms, and laboratory and
endoscopic findings were analyzed to determine the most relevant risk factors. Diagnostic accuracy
and the number of examinations required were estimated and compared with the other 2 algorithms
applied to our series.

1
Department of Digestive Medicine, Hospital Clínic Universitari de València, Universitat de València, Valencia, Spain; 2Department of Digestive Medicine, Hospital
de la Marina Baixa de la Vila Joiosa, Alicante, Spain. Correspondence: Ana Sanahuja, MD. E-mail: anasanahujamar@gmail.com.
Received January 3, 2022; accepted July 29, 2022; published online August 18, 2022

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1594 Tosca et al.

RESULTS: The sample included 532 cases of caustic ingestion, 13.2% (95% confidence interval [CI]: 10.3–16.0)
of which had adverse outcomes. Volume and type of caustic substance; presence of symptoms and
pharyngolaryngeal involvement; and neutrophilia, acidosis, and endoscopic injury were combined to
ENDOSCOPY

develop an algorithm that would provide the highest diagnostic odds ratio (167.2; 95% CI: 71.9–388.7).
Following this approach, half of the patients (50.6%; 95% CI: 46.2–55.1) would not require any
examination and, overall, the need for endoscopy (20.0%; 95% CI: 16.4–23.5) and computed
tomography (16.3%; 95% CI: 13.0–19.5) would be lower than that for the other 2 algorithms.
DISCUSSION: A risk-based algorithm could improve caustic ingestion management by maintaining high diagnostic
accuracy while reducing diagnostic test requirements.
SUPPLEMENTARY MATERIAL accompanies this paper at http://links.lww.com/AJG/C639, http://links.lww.com/AJG/C640, http://links.lww.com/AJG/C641, http://links.
lww.com/AJG/C642, and http://links.lww.com/AJG/C643

Am J Gastroenterol 2022;117:1593–1604. https://doi.org/10.14309/ajg.0000000000001953

INTRODUCTION The study protocol conforms to the ethical guidelines of the

Although most cases are mild, caustic ingestion remains a chal-
lenging clinical scenario whose prognosis is often uncertain and
outcomes can easily become fatal. Identifying patients with poor
prognosis is, therefore, essential to direct treatment (1,2).
Endoscopy has been the cornerstone of the diagnostic ap-
proach for many years and since initial studies by Zargar et al’s
(3–5) has guided patient prognosis and treatment. However,
evidence of the diagnostic superiority of computed tomography
(CT) over endoscopy in detecting transmural necrosis (6) has
changed the paradigm of caustic ingestion management. Al-
though some authors advocate basing therapeutic approach
solely on CT rather than endoscopy (1,7), these results are not
fully supported in all studies (8–10), and the usefulness of both
tests and their role in the diagnostic process have been questioned
(11–13). In line with this idea, several diagnostic algorithms
(1,2,7,12–14) have been proposed for caustic ingestion episodes;
some prioritize CT over endoscopy and others vice versa. How-
ever, all these algorithms have been suggested in an empirical
context, without having been evaluated on diagnostic accuracy.
The hypothesis of our study is that an algorithm developed on the
basis of caustic ingestion risk assessment would improve di-
agnostic accuracy and optimize resource use. Therefore, the aims
of this study were to develop a diagnostic algorithm based on
predictive factors of an adverse clinical course after caustic in-
gestion, evaluate its diagnostic accuracy and diagnostic resource
consumption, and compare this algorithm both with a CT-based
strategy—the radiological algorithm (see Supplementary Mate-
rial, Supplementary Digital Content 1, Figure 1, http://links.lww.
com/AJG/C639) (1)—and with another combined approach
based on the kind of ingestion, symptoms, and endoscopy—the
classical algorithm (see Supplementary Material, Supplementary
Digital Content 2, Figure 2, http://links.lww.com/AJG/C640)(2).
METHODS
Study design
To achieve these aims, we designed an observational and longi-
tudinal study in which variables to be studied for prognostic value
were defined at study start-up, before the start of data collection,
and were prospectively gathered. This study was performed at our
tertiary care center, the Hospital Clínic Universitari de Valencia,
between January 1995 and June 2021, and it comprised a cohort of
patients already included in a previous study on prognostic fac-
tors (15).
1975 Declaration of Helsinki and its later amendments, as
reflected in the approval by the institution’s human research
committee, the Clinical Research Ethics Committee of the Hos-
pital Clinic Universitari de Valencia. We followed STrengthening
the Reporting of OBservational studies in Epidemiology
(STROBE) reporting guidelines for observational studies.
Patients
The accessible population comprised all patients consecutively at-
tending the emergency department of our hospital or referred from
other healthcare centers after caustic ingestion. All these patients
were systematically considered for eligibility using the following
selection criteria: Patients older than 15 years who had ingested any
substance with caustic properties were recruited, excluding cases of
doubtful or nonsignificant intake of a very low volume, particularly
those where the caustic substance was not swallowed or was expelled.
In cases of a single patient with several caustic ingestion incidents, all
different episodes were included. All patients received similar
treatment based on the severity of the clinical situation and endo-
scopic injury; despite the long recruitment period, no major changes
in management of acute episodes of caustic ingestion have occurred,
and relevant variations in the clinical course because of differential
treatment over time are unlikely to have occurred.
Variables
The main variable was adverse outcome, defined by any of the
following: intensive care unit (ICU) admission, need for surgical
treatment, or death. Criteria for ICU admission were sustained
hemodynamic instability despite adequate fluid therapy, re-
spiratory distress despite oxygen replacement, and need for in-
vasive ventilation. Urgent surgery was indicated in cases of clinical,
radiological, or endoscopic evidence of perforation or on clinical
suspicion based on the patient’s progressive clinical impairment.
Clinical, analytical, radiological, and endoscopic variables
were all evaluated for predictive value. All analyzed prognostic
markers were collected following an ad hoc protocol. Clinical
variables were assessed in all patients. Parameters regarding in-
gestion characteristics were also routinely collected, such as the
type of caustic agent, volume, dilution, and pH (weak pH was
defined as values between 2 and 12 and strong pH values less than
or equal to 2 or greater than or equal to 12). Whether ingestion
was accidental or voluntary was also considered. The remaining
clinical variables gathered were symptoms and the presence of

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pharyngeal or laryngeal injury confirmed by an otolaryngology
specialist.
We also systematically studied the role of several analytical
parameters, such as hemoglobin (g/dL), leukocytes (3109/L),
platelets (3109/L), urea (mg/dL), creatinine (mg/dL), electrolytes
(mmol/L), bicarbonate (mEq/L), and pH. According to the study
protocol, arterial blood gas was performed in cases of dyspnea or
oxygen saturation lower than 95% and venous blood gas in the
remaining cases. Radiological tests, such as chest x-ray, abdominal
x-ray, and thoracoabdominal CT with intravenous contrast, were
not systematically performed in all patients but rather at the phy-
sician’s clinical discretion. Radiological examinations were con-
sidered pathological if alterations directly attributable to ingestion
were evidenced, including signs of esophageal or gastrointestinal
perforation or pulmonary involvement due to chemical pneumo-
nitis, aspiration pneumonia, or respiratory distress. After the rel-
evance of CT as a prognostic marker was demonstrated, images
from performed CT scans were reviewed and retrospectively
assigned to that classification (1). Following the study protocol,
urgent endoscopy was proposed in all patients, regardless of in-
gestion severity, and was performed except in cases of patient re-
fusal or contraindication, particularly in cases of severe
otolaryngologic injury, and persistent hemodynamic or respiratory
failure despite treatment or suspected perforation; endoscopic in-
jury was graded in accordance to the Zargar classification (3–5). All
these prognostic variables were collected immediately after the
patient was attended at the emergency department, except the main
variable, which was assessed by an independent researcher at least 3
months after the day of ingestion to ensure that even delayed un-
favorable outcomes were recorded.
Sample size
Because most cases of caustic ingestion have a favorable course,
sample size was calculated to ascertain a specificity of 95%, with
an accuracy of 2% and a confidence level of 95%; the estimated
ratio of patients with a favorable/unfavorable course was 7:1 (15).
With these data, the calculated sample size was 457 cases with a
good clinical course and 66 episodes with adverse outcomes.
Recruitment was continued until both groups reached the esti-
mated sample size.
Statistical analysis
Quantitative variables were described as mean and SD if normal
distribution was present and as median and interquartile range if
not. Normality was studied applying the Kolmogorov-Smirnov test
for groups greater than or equal to 50 or the Shapiro-Wilk test for the
rest. Bivariate analysis of qualitative variables was performed with
the Yates x2 test and alternatively with the Fisher test if at least 20%
had expected values of 5 or less; multiple paired data were compared
by means of the Cochran Q test. Multiple comparisons of variables
were adjusted by means of the Holm-Bonferroni method. Ordinal
variables were studied by a linear-by-linear association, and quan-
titative variables were compared using the Student t test for in-
dependent samples or the Mann-Whitney U test if normal
distribution could not be proved. For quantitative variables, strength
of the association was calculated by simple binary logistic regression
for binary outcomes and was reported as odds ratio (OR) with 95%
confidence interval (CI). To improve clinical applicability, some
continuous variables of interest were dichotomized; the cutoff point
was established by means of the Youden index to optimize sensitivity
and specificity values.
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Caustic Ingestion: A Risk-Based Algorithm 1595
The most promising variables to design the algorithm were
chosen according to bivariate analysis results. Selection was based
on the strength of their association with the main variable and on
their prevalence; in this way, the selected variables were those
ENDOSCOPY
with the highest diagnostic accuracy and which permitted the
number of examinations to be reduced to simplify the algorithm.
Multivariate analysis was subsequently performed with these
potential variables using a manually constructed logistic regression
model (Wald test, complete-case analysis). Priority was given to
maintaining higher predictive ability while minimizing the number
of variables. The model was rated through goodness-of-fit mea-
sures (deviance and Hosmer-Lemeshow test) and predictive ability
tests, such as R-square and area under the receiver operating
characteristic curve. The model obtaining the best scores was
retained; its internal validation was tested by means of a resampling
technique (bootstrapping with 1,500 samples), and a diagnostic
algorithm was designed with the variables included in this model.
For logistic regression analysis, missing data were assumed to
occur at random depending on the severity of ingestion (blood
tests or endoscopy could be lacking in asymptomatic patients). To
minimize the bias that may result from excluding these episodes
from multivariate analysis, multiple imputation was performed to
address missing data recorded in less than 95% of cases: Missing
values were predicted on the basis of logistic and linear regression
analyses for dichotomous and quantitative variables, respectively.
The predictors considered in this multiple-imputation model
were voluntary ingestion and volume taken, presence of psychi-
atric disorder, type of caustic substance, neutrophil count, pH,
grade of endoscopic injury, and main outcome. Twenty different
imputed data sets were generated and combined to obtain an
overall estimate of each regression coefficient and a model per-
formance measure. The predictive value of CT in transmural
necrosis detection was not demonstrated until after elaboration of
the study protocol (6), which did not consider its systematic
implementation in all cases; therefore, the number of patients
undergoing CT included in this study was insufficient to include
this in the multiple-imputation model. It was, therefore, decided
to integrate CT into the final algorithm in cases of high risk of an
unfavorable outcome.
To evaluate their diagnostic accuracy, the 3 algorithms were
then applied to the patients from our series and their expected and
observed outcomes were compared to assess the sensitivity,
specificity, predictive values, likelihood ratios, and diagnostic
ORs of each one. For this purpose, the selected conditions in-
dicating high risk of poor outcomes in each algorithm were as
follows:
ü For the radiological algorithm (see Supplementary Material,
Supplementary Digital Content 1, Figure 1, http://links.lww.
com/AJG/C639): grade 3 in a CT-based classification, defined
as the “absence of esophageal or gastric post-contrast wall
enhancement” (5).
ü For the classical algorithm (see Supplementary Material,
Supplementary Digital Content 2, Figure 2, http://links.lww.
com/AJG/C640): severe endoscopic injury, established as
“small, scattered areas of necrosis, extensive necrosis or
perforation and leading to CT scan and urgent surgical
consultation” (2).
ü For our predictive algorithm: severe endoscopic damage (Zargar grade
III), contraindicated endoscopy or neutrophilia ($75% neutrophil
polymorphonuclear) combined with acidosis (pH , 7.35).
The American Journal of GASTROENTEROLOGY
1596 Tosca et al.

Table 1. Ingestion characteristics, clinical features, and diagnostic tests according to the outcome of caustic ingestion

Overall n 5 532 Favorable outcome n 5 462 Adverse outcome n 5 70 OR (95% CI) P value
ENDOSCOPY

Intake-related variables
Age (yr), median (IR) 48.0 (31) 45.5 (31) 57 (19) 1.02 (1.01–1.04) 0.001
Sex, n (%) 0.871
Female 265 (49.8) 229 (86.4) 36 (13.6) 0.93
Male 267 (50.2) 233 (87.3) 34 (12.7) (0.56–1.54)
pH of substance, n (%)
Strong acid 84 (15.8) 35 (41.7) 49 (58.3) 37.20 (18.70–73.99) ,0.001
Weak acid 29 (5.5) 27 (93.1) 2 (6.9) 1.97 (0.43–9.11) 0.378
Weak alkali 386 (72.6) 372 (96.4) 14 (3.6) — —
Strong alkali 21 (3.9) 18 (85.7) 3 (14.3) 4.43 (1.17–16.81) 0.034
Unknown 12 (2.3)
Volume, n (%) ,0.001
,200 mL 399 (75.0) 364 (91.2) 35 (8.8) 4.41
$200 mL 94 (17.7) 66 (70.2) 28 (29.8) (2.52–7.74)
Unknown 39 (7.3)
Voluntary ingestion, n (%) ,0.001
No 274 (51.5) 268 (97.8) 6 (2.2) 14.51
Yes 257 (48.3) 194 (75.5) 63 (24.5) (6.15–34.19)
Unknown 1 (0.2)
Symptoms and physical examination
Psychiatric disorder, n (%) ,0.001
No 281 (52.8) 267 (95.0) 14 (5.0) 5.48
Yes 251 (47.2) 195 (77.7) 56 (22.3) (2.96–10.12)
No. of symptoms, n (%)
None 119 (22.4) 119 (0.0) 0 (0.0) — —
1 or 2 221 (41.5) 199 (90.0) 22 (10.0) 1.11 (1.06–1.16) 0.001
3 or 4 122 (22.9) 102 (83.6) 20 (16.4) 1.20 (1.11–1.29) ,0.001
5 or more 70 (13.2) 42 (60.0) 28 (40.0) 1.67 (1.38–2.02) ,0.001
Oropharyngeal injury, n (%) ,0.001
No 281 (52.8) 273 (97.2) 8 (2.8) 11.70 (5.46-25.06)
Yes 235 (44.2) 175 (74.5) 60 (25.5)
Unknown 16 (3.0)
Laryngeal injury, n (%) ,0.001
No 375 (70.5) 358 (95.5) 17 (4.5) 11.38 (6.23-20.77)
Yes 134 (25.2) 87 (64.9) 47 (35.1)
Unknown 23 (4.3)
Blood test
Hemoglobin (g/dL), median (IR) 13.8 (2.1) 13.8 (3.4) 1.01 (0.98–1.04) 0.582
Unknown 82 (15.4)
Leukocytes, n (%) ,0.001
,12.0 (109/L) 326 (93.7) 22 (6.3) 10.46
$12.0 (109/L) 68 (58.6) 48 (41.4) (5.93–18.47)
Unknown 68 (12.8)
Neutrophil count, n (%) ,0.001
,75% 290 (96.0) 12 (4.0) 14.81
$75% 93 (62.0) 57 (38.0) (7.62–28.80)
Unknown 75 (14.1)
Urea (mg/dL), median (IR) 79 (14.8) 32 (16.0) 36 (18.0) 1.01 (1.00–1.03) 0.009
Unknown
Creatinine (mg/dL), median (IR) 0.80 (0.30) 0.92 (0.42) 2.77 (1.16–6.64) 0.032
Unknown 77 (14.5)

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 Caustic Ingestion: A Risk-Based Algorithm 1597

Table 1. (continued)

Overall n 5 532 Favorable outcome n 5 462 Adverse outcome n 5 70 OR (95% CI) P value

ENDOSCOPY
pH, n (%)
Normal 305 (57.3) 285 (93.4) 20 (6.6) — —
Acidosis 90 (16.9) 42 (46.7) 48 (53.3) 16.29 (8.81-30.09) ,0.001
Alkalosis 40 (7.5) 38 (95.0) 2 (5.0) 0.75 (0.17-3.34) 1.000
Unknown 97 (18.2)
Radiology
Chest x-ray, n (%)
Normal 457 (85.9) 406 (88.8) 51 (11.2) 22.29 ,0.001
Impaired 19 (3.6) 5 (26.3) 13 (73.7) (7.71–64.46)
Not performed 56 (10.5)
Abdomen x-ray, n (%)
Normal 385 (72.4) 340 (88.3) 45 (11.7) 30.22 ,0.001
Impaired 10 (1.9) 2 (20.0) 8 (80.0) (6.22–146.78)
Not performed 137 (25.8)
Computed tomography, n (%)
Grade 1 5 (0.9) 4 (80.0) 1 (20.0) — —
Grade 2 8 (1.5) 3 (37.5) 5 (62.5) 6.67 (0.49–91.33) 0.266
Grade 3 14 (2.6) 3 (21.4) 11 (78.6) 14.67 (1.16–185.24) 0.038
Not performed 505 (94.9)
Endoscopy
Endoscopy, n (%)
Performed 441 (82.9) 384 (87.1) 57 (12.9) — —
Not performed
Nonrelevant intake 42 (7.2) 42 (100.0) 0 (0.0) — 0.03
Patient refusal 15 (2.8) 15 (100.0) 0 (0.0) — 0.470
Contraindication 17 (3.2) 5 (29.4) 12 (70.6) 16.2 (5.5–47.6) ,0.001
Other/unknown reason 17 (3.2) 16 (94.1) 1 (5.9) 0.4 (0.1–3.2) 0.709
a
Esophageal injury , n (%)
0 229 (51.9) 225 (98.3) 4 (1.7) — —
I 79 (17.9) 75 (94.9) 4 (5.1) 3.00 (0.73–12.92) 0.235
IIa 62 (14.1) 55 (88.7) 7 (11.3) 7.16 (2.02–25.32) 0.004
IIb 44 (10.0) 28 (63.6) 16 (36.4) 32.14 (10.03–102.94) ,0.001
III 27 (6.1) 1 (3.7) 26 (96.3) 1,462.50 (157.48–13581.99) ,0.001
Gastric injurya, n (%)
0 160 (36.3) 158 (98.8) 2 (1.3) — —
I 111 (25.2) 109 (98.2) 2 (1.8) 1.45 (0.20-10.45) 1.000
IIa 72 (16.3) 66 (91.7) 6 (8.3) 7.18 (1.41-36.50) 0.057
IIb 36 (8.2) 34 (94.4) 2 (5.6) 4.65 (0.63-34.16) 0.636
III 61 (13.8) 16 (26.2) 45 (73.8) 222.19 (49.24-1002.59) ,0.001
Not assessed 1 (0.2)
Duodenal injury a, n (%)
0 340 (77.3) 325 (95.6) 15 (4.4) — —
I 45 (10.2) 37 (82.2) 8 (17.8) 4.68 (1.86–11.79) 0.002
IIa 14 (3.2) 9 (64.3) 5 (35.7) 12.04 (3.59–40.35) ,0.001

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1598 Tosca et al.

Table 1. (continued)

Overall n 5 532 Favorable outcome n 5 462 Adverse outcome n 5 70 OR (95% CI) P value
ENDOSCOPY

IIb 12 (2.7) 5 (41.7) 7 (58.3) 30.33 (861–106.83) ,0.001

III 8 (1.8) 1 (12.5) 7 (87.5) 151.67 (17.52–1,312.86) ,0.001
Not assessed 21 (4.8)
Extent of injury, n (%)
No injury 121 (27.4) 121 (100) 0 (0.0) — —
Esophagus 40 (9.1) 38 (95.0) 2 (5.0) — 0.061
Stomach 108 (24.5) 104 (96.3) 4 (3.7) — 0.096
Both 172 (39.0) 121 (70.3) 51 (29.7) — ,0.001

In the case of continuous quantitative variables, the odds ratio is expressed per one-unit increase.
CI, confidence interval; IR, interquartile range; OR, odds ratio.
a
Zargar classification.

Finally, we calculated the number of tests required according to
each algorithm implemented in our series to estimate the di-
agnostic resource consumption of each strategy in real life. For this
goal, ingestion of over 200 mL of caustic was considered “massive
ingestion” (1), patients presenting 1 or 2 symptoms were classified
as “minimally symptomatic,” and defining “critically ill” (2) pa-
tients was left to clinician judgement.
All P-values were 2-sided, and the global significance level was
fixed at P # 0.05. Statistical analysis was performed using IBM
SPSS Statistics, version 26.0.
Patient and public involvement
No patients and the public were involved in the design, conduct,
reporting, and dissemination plans of this research.
RESULTS
The recruitment period included 532 episodes of caustic ingestion
in 488 patients (453 single-ingestion episodes; 35 patients rep-
resented 2 or more episodes). The median age was 48 years
(interquartile range: 31 years), and the sex ratio was as expected
(49.8% women and 50.2% men, P 5 0.931).
The caustic agent ingested was alkaline in 407 cases (76.5%; 95%
CI: 72.9–80.1), acidic in 113 cases (21.2%; 95% CI: 17.8–24.7), and in
the remaining 12 episodes, the pH of the substance involved could not
be identified (2.3%; 95% CI: 1.0–3.5). Overall, most of the ingestions
(462) had a favorable outcome (86.8%; 95% CI: 84.0–89.7), although
66 ingested patients were admitted to ICU (12.4%; 95% CI: 9.6–15.2),
17 patients required emergency surgery (3.2%; 95% CI: 1.7–4.7), and
28 patients died during the acute episode (5.3%; 95% CI: 3.4–7.2). The
clinical, analytical, radiological, and endoscopic features of ingestion
are summarized in Table 1 by episode outcome. The symptoms taken
into consideration in the analysis are detailed in Supplementary
Material (see Supplementary Digital Content 4, Table 1, http://links.
lww.com/AJG/C642).
endoscopy (see Supplementary Material, Supplementary Digital
Content 5, Table 2, http://links.lww.com/AJG/C643). The com-
bination of neutrophilia and acidosis enabled a reliable assess-
ment of prognosis per se (Figure 1).
The goodness of fit of the predictive model was estimated by
deviance (95.7) and the Hosmer-Lemeshow test (5.87; P 5 0.556); its
predictive ability was evaluated by means of R-square (0.803) and the
receiver operating characteristic curve (see Supplementary Material,
Supplementary Digital Content 3, Figure 3a, http://links.lww.com/
AJG/C641), which yielded an area under the curve of 0.982 (95% CI:
0.972–0.993).
To assess the effect of the timing of endoscopy, the model’s
performance was compared for early (first 6 hours) and late (more
than 6 hours after ingestion) endoscopy; the 2 areas under the curve
were similar (0.988; 95% CI: 0.973–1.000 and 0.978; 95% CI:
0.961–0.996, respectively, with P 5 0.409, see Supplementary
Material, Supplementary Digital Content 3, Figure 3b, http://links.
lww.com/AJG/C641).
Risk assessment and algorithm development
The selected variables were then sequentially combined to define
6 different groups according to risk of poor outcome (Figure 2).
Ingestions with null risk (0%) of complications comprised low-
volume ingestion of weak caustic substance without pharyngeal
or laryngeal injury, and any kind of ingestion provided to the

Poor prognostic variables

On multivariate analysis, the variables with best diagnostic per-
formance in algorithm construction were massive ingestion
($200 mL) of strong caustic substances (pH , 2 or pH . 12);
presence of symptoms and pharyngeal or laryngeal injury on
examination; neutrophilia/acidosis and severe injury (grade III Figure 1. Risk of poor outcomes of the different combinations of blood
according to the Zargar classification); and contraindication to tests. ICU, intensive care unit.

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 Caustic Ingestion: A Risk-Based Algorithm 1599

ENDOSCOPY

Figure 2. Outcomes of caustic ingestion episodes based on their predictive factors.

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1600
ENDOSCOPY Tosca et al.

Figure 3. Risk-based algorithm for caustic ingestion. 1. Weak caustic substance 2 , pH , 12; 2. Low volume #200 mL.

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Table 2. Diagnostic accuracy of different algorithms for any adverse outcome (ICU admission, surgery, or death)
Sensitivity % Specificity %
(95% CI) (95% CI)
Radiological algorithm (1) 64.7 70.0
(41.3–82.7) (39.7–89.2)
Classical algorithm (2) 51.4 98.7
(40.0–63.1) (97.2–99.4)
Predictive algorithm 87.1 96.1
(77.3–93.0) (93.9–97.5)
CI, confidence interval; ICU, intensive care unit; OR, odds ratio.
patient remained asymptomatic. Symptomatic patients who had
neither neutrophilia nor acidosis and those with neutrophilia or
acidosis but mild endoscopic injury (Zargar grade # IIb) had a
low risk of adverse outcome (5%). High-risk ingestions (.60%)
were those with symptoms, neutrophilia or acidosis, and severe
endoscopic injury (Zargar grade III) or contraindication to en-
doscopy and those with symptoms and both neutrophilia and
acidosis. A diagnostic algorithm was then developed on the basis
of the level of risk of adverse outcome for each group (Figure 3).
Comparison between different algorithms
Diagnostic accuracy. The predictive algorithm had significantly
higher sensitivity than the other 2 for detecting any adverse outcome,
and the specificity of the classical and predictive approaches were
better than the radiological one (Table 2). Both the classical (80.5;
95% CI: 31.7–204.3) and predictive (167.2; 95% CI: 71.9–388.7)
approaches had significantly higher diagnostic ORs than the ra-
diological strategy (4.3; 95% CI: 0.8–22.9). The sensitivity and
specificity of each independent outcome are detailed in Figure 4.
Diagnostic resource consumption
The proportion of patients requiring no examination was significantly
higher for the predictive algorithm (50.6%; 95% CI: 46.2%–55.1%)
than for the classical one (34.5%; 95% CI: 30.5%–38.6%) or the ra-
diological strategy (0.0%; 95% CI: 0.0%–0.0%) (Figure 5).
Although a higher number of blood tests was required for our
predictive algorithm (49.4%; 95% CI: 44.9%–53.8%) than for the
other 2 (19.1%; 95% CI: 15.6%–22.5% for the radiological al-
gorithm and in critically ill patients only for the classical one),
this approach reduced the number of the other 2 diagnostic
tests. Thus, a lower number of endoscopies were performed
overall for the predictive algorithm (20.0%; 95% CI:
16.4%–23.5%) and the radiological one (29.6%; 95% CI:
12.4%–46.9%), and the number of CT scans needed was sig-
nificantly reduced following both the classical (13.4%; 95% CI:
10.5%–16.3%) and predictive (16.3%; 95% CI: 13.0%–19.5%)
strategies.
DISCUSSION
Our data show that a risk-based algorithm could optimize caustic
ingestion management by maintaining high diagnostic accuracy
while reducing the number of tests required. By guiding di-
agnostic sequence according to the pretest probability of poor
outcomes, we could restrict examinations to patients with a sig-
nificant risk of complication.
© 2022 by The American College of Gastroenterology
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Caustic Ingestion: A Risk-Based Algorithm 1601
Negative
ENDOSCOPY
Positive Negative Positive likelihood
predictive value predictive value likelihood ratio ratio Diagnostic OR
78.6 53.8 2.2 0.5 (0.2–1.1) 4.3
(57.1–100) (26.7–80.9) (0.8–5.9) (0.8–22.9)
85.7 93.1 39.6 0.5 (0.4–0.6) 80.5
(75.1–96.3) (90.8–95.3) (17.3–90.5) (31.7–204.3)
77.2 98.0 22.4 0.1 (0.1–0.2) 167.2
(68.0–86.5) (96.7–99.3) (14.1–35.5) (71.9–388.7)
The value of symptoms and pharyngeal or laryngeal injury has
previously been controversial: For some authors, neither is related
to episode severity (3,5,16,17), whereas for others, both may be
associated with a more complicated ingestion (18–25). These dis-
crepancies could be explained by methodologic issues and by the
fact that many of these studies examine their value as individual
predictors of adverse outcomes; in our series, however, combining
these variables with data on the ingestion pattern (volume and pH)
improves prediction accuracy and, in addition, solely their ability to
detect cases of positive outcome is considered, rather than their
overall diagnostic accuracy. This result proves to be very useful as a
first step in the assessment because it accurately identifies a sub-
stantial patient subset who will have an uncomplicated disease
course and implies that around 50% of caustic ingestion cases
would not need any examination and could be safely discharged.
In the remaining half of the cases, the combination of neutro-
philia and acidosis provides a stratification of the risk of poor
outcome and enables us to guide diagnostic tests according to that
risk; if it is low, no other test would be necessary again, and in cases
of moderate or high risk, endoscopy or CT would be performed,
respectively. In this way, the diagnostic performance of each test is
complemented in an additive manner.
In recent years, the usefulness of endoscopy in caustic ingestion
management has been questioned (7,11,13,26,27), largely because
of its principal limitation: Injury assessment is strictly limited to the
mucosa, without revealing damage to the deeper layers of the
gastrointestinal tract. This limitation can be overcome by other
techniques, such as ultrasound endoscopy (28,29) and CT (9,10),
because both have shown that transmural involvement is associ-
ated with worse short-term prognosis.
Recent studies have revealed CT to be more effective than en-
doscopy alone in detecting transmural necrosis and predicting the
need for urgent surgery (6,30), with the result that CT has even been
advocated as the cornerstone of diagnosis and management of
caustic ingestion (1). However, the problem with this diagnostic
approach is the potential selection bias toward a population with an
urgent need for surgery (20%); in populations with a low prevalence
of surgery (according to the real-world data of our series, 3.2%), its
predictive value is significantly reduced, and this strategy implies
performing a large number of unnecessary CT scans.
Conversely, in a previous study, we showed that combining
endoscopy with several clinical and analytical data can also sig-
nificantly extend the practice of endoscopy alone (15). In this
setting, neutrophilia reflects a systemic inflammatory response
and acidosis would indicate tissue necrosis; both alterations
The American Journal of GASTROENTEROLOGY
1602
ENDOSCOPY Tosca et al.

Figure 4. Sensitivity (a) and specificity (b) of the algorithms for the different outcomes.

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Figure 5. Supplementary tests required depending on the type of algorithm. CI, confidence interval; CT, computed tomography.
considered indicators of transmural necrosis, completing the
endoscopic mucosal assessment.
At this stage, the importance of these analytical findings as
screening tests for complications cannot be understated. Their ability
to recognize patients at risk of a poor clinical course allows us to restrict
CT to patients at higher risk (neutrophilia and acidosis), thereby in-
creasing the pretest probability in this group of patients, improving
their predictive value and avoiding unnecessary procedures in patients
who will otherwise have a mild disease course. Patients with a medium
risk of complications (neutrophilia or acidosis) would require en-
doscopy to assess their prognosis; in fact, in this setting, endoscopy
seems more accurate than CT in differentiating moderate mucosal
inflammation, which is still at risk of complication (1).
With this approach, endoscopy and CT are no longer mutually
exclusive but can coexist in the diagnostic workup of ingestion by
targeting patients with different prognoses. In this way, CT and en-
doscopy are performed in patient subsets with a sufficient prevalence of
adverse outcomes to justify the utility of each examination. Therefore,
this algorithm optimizes the diagnostic workflow, reducing the num-
ber of these examinations and increasing their diagnostic efficiency.
The main limitation of this study is the reduced number of CT
scans included. Although some authors suggest that up to 90% of
missing data could be adjusted by multiple imputations (31), CT
scan was judged unsuitable for this technique as one of the main
variables under evaluation. Our accuracy analysis was, therefore,
restricted to existing data collected in our series where CT was
performed by clinical indication rather than by protocol, meaning
that although valid, the assessment of the diagnostic yield of the CT-
based strategy is less precise for the indicators not dependent on
disease prevalence (sensitivity, specificity, and positive and negative
likelihood ratios and diagnostic ORs). Moreover, because CT was
not performed systematically but only in clinically severe cases, its
positive and negative predictive values may have been overestimated
and underestimated, respectively, and finally, the small sample size
© 2022 by The American College of Gastroenterology
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Caustic Ingestion: A Risk-Based Algorithm 1603
ENDOSCOPY
may probably also explain the lack of differences in endoscopy
requirements between CT-based and risk-based algorithms.
Nonetheless, this drawback is not a hindrance either to ana-
lyzing the diagnostic accuracy of the other two algorithms (the
variables indicating high risk of poor outcome were severe en-
doscopic injury and neutrophilia with acidosis) or to estimating
diagnostic requirements for any of the 3 strategies.
As an advantage, our study does not limit adverse outcomes
to emergency surgery, but rather encompasses all 3 clinically
relevant adverse clinical courses, giving it wider applicability in
practice when it is necessary to pinpoint with precision patients
who will have a complicated disease course. Because approxi-
mately half of the patients would not require any diagnostic
tests, the new algorithm could also serve as criteria for referring
patients from primary care departments or home emergencies
to tertiary hospitals for further tests. As a relatively large and
consecutive patient series, it includes all cases consulting for
caustic ingestion, so its external validity would not be limited by
episode severity but would be restricted to the adult population,
so the results could not be directly extrapolated to the pediatric
population.
Building an algorithm that enables patient test selection on the
basis of risk of complication could reduce the need for tests, simul-
taneously optimizing their diagnostic capacity. However, although
this strategy seems theoretically more effective, external validation in
different patient series is warranted to confirm its utility.
DATA SHARING
Beginning 3 months and ending 5 years after article publication,
deidentified participant data might be made available to investi-
gators whose proposed use of the data has been approved by a
review committee. The study protocol will also be available. Pro-
posals should be directed to joantosca@gmail.com; to gain access to
data, requestors will need to sign a data access agreement.
The American Journal of GASTROENTEROLOGY
1604 Tosca et al.
ACKNOWLEDGMENTS
We dedicate this work to Adolfo Benages (1942–2012).
ENDOSCOPY
CONFLICTS OF INTEREST
Guarantor of the article: Joan Tosca, MD, PhD.
Specific author contributions: J.T., A.S., and A.S. contributed to the
design of the study, drafting of the manuscript, study supervision, data
collection, analysis and interpretation, and final responsibility for the
decision to submit for publication. R.V., P.M., I.P., P.L., A.P., V.S., and
M.M. participated in critical revision of the manuscript and provided
critical feedback on methods or results. All authors had full access to all
the data in the study and approved manuscript publication. P.P. and
B.H. contributed to data collection, analysis, and interpretation.
Financial support: None to report.
Potential competing interests: None to report.
Study Highlights
WHAT IS KNOWN
3 The role of endoscopy in the management of caustic ingestion
has been challenged, after the publication of studies
supporting the greater ability of computed tomography (CT) to
detect transmural necrosis.
3 However, the prevalence of complications in these studies is
greater than in real life, where CT may not be the optimal initial
examination.
3 An algorithm developed on the basis of risk assessment would
improve diagnostic accuracy and optimize resource use.
WHAT IS NEW HERE
3 To the best of our knowledge, the resulting algorithm is the first to
be based on the individual risk assessment of the intake to
determine which is the most suitable examination in every case.
3 Stratifying the risk of each intake enables to select the optimal
examination depending on the pretest probability of an
adverse outcome.
3 According to this strategy, the sensitivity and specificity of the
clinical data and the different tests complement themselves in
an additive way so that the overall accuracy of the algorithm
improves while reducing the number of tests.
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