Japanese guidelines for the management of intussusception in children, 2011

Authors


Yasuo Ito, MD PhD, Department of Pediatric Surgery, International University of Health and Welfare, Atami Hospital, 13-1 Higashikaigancho, Atami, Shizuoka 413-0012, Japan. Email: yasuito@iuhw.ac.jp

Abstract

Background:  The Japanese Society of Emergency Pediatrics has formulated evidence-based guidelines for the management of intussusception in children in order to diagnose intussusceptions promptly, to initiate appropriate treatment as early as possible, and to protect intussuscepted children from death.

Methods:  Literature was collected systematically via the Internet using the key words “intussusception” and “children.” The evidence level of each paper was rated in accordance with the levels of evidence of the Oxford Center for Evidence-based Medicine. The guidelines consisted of 50 clinical questions and the answers. Grades of recommendation were added to the procedures recommended on the basis of the strength of evidence levels.

Results:  Three criteria of “diagnostic criteria,”“severity assessment criteria,” and “criteria for patient transfer” were proposed aiming at an early diagnosis, selection of appropriate treatment, and patient transfer for referral to a tertiary hospital in severe cases. Barium is no longer recommended for enema reduction (recommendation D) because the patient becomes severely ill once perforation occurs. Use of other contrast media, such as water-soluble iodinated contrast, normal saline, or air, is recommended under either fluoroscopic or sonographic guidance. Delayed repeat enema improves reduction success rate, and is recommended if the initial enema partially reduced the intussusception and if the patient condition is stable.

Conclusions:  The guidelines offer standards of management, but it is not necessarily the purpose of the guidelines to regulate clinical practices. One should judge each individual clinical situation in accordance with experiences, available devices, and the patient's condition.

Background, purpose, method of formulation, and notes on usage

Background of the development of the guidelines

In 2004, the Japanese Society of Emergency Pediatrics organized a guideline committee to develop evidence-based guidelines for the management of intussusception in children. In 2011, the draft of the guidelines was proposed at the annual meetings of the Japan Pediatric Society, the Japanese Society of Pediatric Surgeons, and the Japanese Society of Pediatric Radiology, as well as the Japanese Society of Emergency Pediatrics. The guidelines were completed with the consensus of these related societies.

The guideline committee consisted of four pediatricians, five pediatric surgeons, and one external examiner, all of whom were listed as authors.

Purpose of the guidelines

Intussusception is one of the most common causes of pediatric emergencies. Delay in diagnosis and treatment may result in bowel necrosis or even death of infants and children; however, there are no previous clinical guidelines for the management of this condition, neither in Japan nor in other countries. For more than a century the gold standard for the management of intussusception has been barium enema reduction under fluoroscopic control; however, nowadays there are numerous different methods of management, and the procedures employed depend on the personal preference and experiences of the clinician responsible for the care of the child, causing confusion at the site of medical practices.

The purposes of these guidelines are to guide clinicians in order to diagnose intussusceptions promptly, to initiate appropriate treatment as early as possible, and to protect intussuscepted children from bowel necrosis, perforation, shock, and death.

Methods of formulating the guidelines

The guidelines were prepared using the technique of evidence-based medicine. English-language literature was collected from PubMed (Ovid; 1966 to September 2009) using the key words “intussusception” and “child” or “children,” with the limiting words “human” and “English.” Japanese literature was collected from the Internet version of the Japana Centra Revuo Medicina (Nippon Igaku Chuuou Zasshi; Ovid; 1983 to September 2009) with the equivalent key words. A total of 2033 papers were collected (1275 in English and 758 in Japanese), including papers selected from references. First, the titles and abstracts of all papers were examined, and 616 important papers were chosen for a careful examination of their full texts. Each paper was independently evaluated by two examiners, and the evidence level of the paper was rated in accordance with the Levels of Evidence of the Oxford Center for Evidence-Based Medicine (see the section “Categories of evidence levels and grading for recommendations”). Then, papers that were rated above level 3 were reevaluated critically by three examiners, including the committee chairman, and the final evidence level was determined at a committee meeting in cases where there was disagreement among the examiners.

Notes on the usage of the guidelines

The guidelines consisted of 50 clinical questions (CQ) and answers (A) to these questions related to epidemiology, diagnosis, assessment of severity, and treatment. Evidence levels were indicated for the quoted literature, and grades of recommendation were added to the procedures recommended. In principle, the decision for recommendation was based on the strength of evidence levels, but social factors, such as medical environment, cost performance, and the Japanese Health Insurance System, also had to be considered in light of a paucity of randomized control studies and prospective studies on this condition.

The guidelines offer standards of management, but it is not necessarily the purpose of the guidelines to regulate clinical practices. One should judge each individual clinical situation in accordance with staff numbers, experiences, available devices, and the patient's condition. The committee owes responsibility to the contents of the guidelines, but does not owe responsibility to the results of individual cases.

Notes on the usage of the guidelines in foreign countries

The original guidelines are written in Japanese.1 This is an abbreviated English translation of the Japanese edition of “Evidence-based Guidelines for the Management of Intussusception in Children.”

These guidelines are aimed to be used specifically in Japan, but some portions may be of value in foreign countries as well; however, readers should be aware that these guidelines reflect the Japanese medical environment, including the health insurance system. First, the health insurance system in Japan allows patients free access to hospitals without limitation. The majority of patients with intussusceptions visit clinics or hospitals in a timely fashion and are seen primarily by pediatricians and/or pediatric surgeons from the beginning of their treatment. It is very rare that pediatric radiologists join in the team. Second, medical expenses of infants and children are covered by health insurance and municipal medical aids, and therefore families do not need to pay fees at all in most cases. It is advised that these guidelines should be modified when they are used in foreign countries to fit their medical environments.

Categories of evidence levels and grading for recommendations

Categories and levels of evidence

The evidence level of each paper was rated in accordance with the Oxford Center for Evidence-Based Medicine Levels of Evidence2 (May 2009)3 (Table 1).

Table 1. Categories and levels of evidence by Oxford Center for Evidence-Based Medicine
LevelTherapy / prevention, cause / harmPrognosisDiagnosisDifferential diagnosis / symptom prevalence studyEconomic and decision analyses
  • (Produced by Bob Phillips, Chris Ball, Dave Sackett, Doug Badenoch, Sharon Straus, Brian Haynes, Martin Dawes since November 1998. Updated by Jeremy Howick March 2009.)

  • Notes:

  • a

    By homogeneity we mean a systematic review that is free of worrisome variations (heterogeneity) in the directions and degrees of results between individual studies. Not all systematic reviews with statistically significant heterogeneity need be worrisome, and not all worrisome heterogeneity need be statistically significant. As noted above, studies displaying worrisome heterogeneity should be tagged with a “−” at the end of their designated level.

  • b

    Clinical Decision Rule. (These are algorithms or scoring systems that lead to a prognostic estimation or a diagnostic category.)

  • c

    See note above for advice on how to understand, rate and use trials or other studies with wide confidence intervals.

  • d

    Met when all patients died before the Rx became available, but some now survive on it; or when some patients died before the Rx became available, but none now die on it.

  • e

    By poor quality cohort study we mean one that failed to clearly define comparison groups and/or failed to measure exposures and outcomes in the same (preferably blinded), objective way in both exposed and non-exposed individuals and/or failed to identify or appropriately control known confounders and/or failed to carry out a sufficiently long and complete follow up of patients. By poor quality case–control study we mean one that failed to clearly define comparison groups and/or failed to measure exposures and outcomes in the same (preferably blinded), objective way in both cases and controls and/or failed to identify or appropriately control known confounders.

  • f

    Split-sample validation is achieved by collecting all the information in a single tranche, then artificially dividing this into “derivation” and “validation” samples.

  • g

    An “Absolute SpPin” is a diagnostic finding whose Specificity is so high that a Positive result rules in the diagnosis. An “Absolute SnNout” is a diagnostic finding whose Sensitivity is so high that a Negative result rules out the diagnosis.

  • h

    Good reference standards are independent of the test, and applied blindly or objectively to all patients. Poor reference standards are haphazardly applied, but still independent of the test. Use of a non-independent reference standard (where the “test” is included in the “reference,” or where the “testing” affects the “reference”) implies a level 4 study.

  • i

    Better-value treatments are clearly as good but cheaper, or better at the same or reduced cost. Worse-value treatments are as good and more expensive, or worse and equally or more expensive.

  • j

    Validating studies test the quality of a specific diagnostic test, based on prior evidence. An exploratory study collects information and trawls the data (e.g. using a regression analysis) to find which factors are “significant.”

  • k

    By poor-quality prognostic cohort study we mean one in which sampling was biased in favor of patients who already had the target outcome, or the measurement of outcomes was accomplished in <80% of study patients, or outcomes were determined in an unblinded, non-objective way, or there was no correction for confounding factors.

  • l

    Good follow up in a differential diagnosis study is >80%, with adequate time for alternative diagnoses to emerge (for example 1–6 months acute, 1–5 years chronic).

1aSR (with homogeneitya) of RCTSR (with homogeneitya) of inception cohort studies; CDRb validated in different populationsSR (with homogeneitya) of level 1 diagnostic studies; CDRb with 1b studies from different clinical centersSR (with homogeneitya) of prospective cohort studiesSR (with homogeneitya) of level 1 economic studies
1bIndividual RCT (with narrow confidence intervalc)Individual inception cohort study with > 80% follow up; CDRb validated in a single populationValidatingj cohort study with goodh reference standards; or CDRb tested within one clinical centreProspective cohort study with good follow uplAnalysis based on clinically sensible costs or alternatives; systematic review(s) of the evidence; and including multi-way sensitivity analyses
1cAll or nonedAll or none case-seriesAbsolute SpPins and SnNoutsgAll or none case-seriesAbsolute better-value or worse-value analysesi
2aSR (with homogeneitya) of cohort studiesSR (with homogeneitya) of either retrospective cohort studies or untreated control groups in RCTSR (with homogeneitya) of level >2 diagnostic studiesSR (with homogeneitya) of 2b and better studiesSR (with homogeneitya) of level >2 economic studies
2bIndividual cohort study (including low-quality RCT; e.g., <80% follow up)Retrospective cohort study or follow up of untreated control patients in an RCT; derivation of CDRb or validated on split-samplef onlyExploratoryj cohort study with goodh reference standards; CDRb after derivation, or validated only on split-samplef or databasesRetrospective cohort study, or poor follow upAnalysis based on clinically sensible costs or alternatives; limited review(s) of the evidence, or single studies; and including multi-way sensitivity analyses
2c“Outcomes” research; ecological studies“Outcomes” research Ecological studiesAudit or outcomes research
3aSR (with homogeneitya) of case–control studies SR (with homogeneitya) of 3b and better studiesSR (with homogeneitya) of 3b and better studiesSR (with homogeneitya) of 3b and better studies
3bIndividual case–control Study Non-consecutive study; or without consistently applied reference standardsNon-consecutive cohort study, or very limited populationAnalysis based on limited alternatives or costs, poor quality estimates of data, but including sensitivity analyses incorporating clinically sensible variations.
4Case-series (and poor quality cohort and case–control studiese)Case-series (and poor quality prognostic cohort studiesk)Case–control study, poor or non-independent reference standardCase-series or superseded reference standardsAnalysis with no sensitivity analysis
5Expert opinion without explicit critical appraisal, or based on physiology, bench research or “first principles”Expert opinion without explicit critical appraisal, or based on physiology, bench research or “first principles”Expert opinion without explicit critical appraisal, or based on physiology, bench research or “first principles”Expert opinion without explicit critical appraisal, or based on physiology, bench research or “first principles”Expert opinion without explicit critical appraisal, or based on economic theory or “first principles”

Grading system for recommendations

Based on the evidence levels of literature, a grade of recommendation was determined for each medical procedure in accordance with the following grading system, which is a modification of “Recommendation Grades 2007” of the Medical Information Network Service in Japan (Table 2).4

Table 2. Grading system for rating recommendations
GradeType of recommendation
AStrong recommendation to perform this procedure
There is good evidence to support its clinical effects.
BFair recommendation to perform this procedure
There is fair evidence to support its clinical effects.
C1Poor recommendation to perform this procedure
The existing evidence is poor, but there is a possibility of favorable effects.
C2Recommendation undetermined
The existing evidence is poor or conflicting, and does not allow for making a clear recommendation.
DRecommendation not to perform this procedure
There is evidence to deny its usefulness, or to show its adverse effects.

Definition

Intussusception

Intussusception is the invagination of the proximal bowel into the distal bowel, causing intestinal obstruction. The mesenteric vessels are drawn into the intussuscipiens as well, leading to a strangulating obstruction. Most cases are “idiopathic,” which means there is no obvious cause other than lymphoid hyperplasia of the terminal ileum. In some cases, invagination is obviously secondarily induced by an identifiable cause (pathological lead point; PLP) or underlying systemic disease. Intussusception in the postoperative period is typically due to dysmotility of the intestine after surgery.

Types

Intussusceptions are classified into five types in these guidelines: ileocolic, ileoileocolic, enteroenteric (including jejunojejunal and ileoileal), and colocolic types. The ileocolic type is most common, and the majority of ileocolic intussusceptions are idiopathic. The term intussusception in the guidelines mostly refers to “idiopathic ileocolic type,” except where otherwise indicated.

Reductions

There are two methods for reduction of intussusception: non-operative and operative. In non-operative reduction the apex of the intussusceptum is pushed back by hydrostatic or pneumatic enema. Different types of contrast media (including negative contrast of air) are used under the guidance of fluoroscopy or sonography. Various combinations of contrast media and monitoring modalities are possible. In these guidelines, the term “enema reduction” is used to represent hydrostatic and pneumatic reduction. Operative reduction refers to the Hutchinson procedure by laparotomy in general, but recent laparoscopic reduction is an alternative.

Delayed repeat enema

Delayed repeat enema refers to the reattempt of enema reduction at a certain time interval after the initial attempt at reduction was a failure. There are many other synonyms, such as repeat delayed enema, delayed repeated enema, delayed repeated attempted enema, delayed attempt reduction, repeated delayed reduction attempt, etc. Delayed repeat enema generally refers to the reattempt of reduction at the same institution.

Flowchart for the management of intussusception in children

A flowchart for the management of intussusception in children is presented in Figure 1. The details of diagnostic criteria, severity criteria, and criteria for patient transport for referral are described in CQ8, CQ19, and CQ27, respectively.

Figure 1.

A flowchart for the management of intussusception in children. DRE, delayed repeat enema; ICU, intensive care unit.

Epidemiology

A population-based epidemiologic study of intussusception is essential in order for a state or a country to know the baseline incidence of this condition prior to introduction of rotavirus vaccination. Unfortunately, a nationwide epidemiologic study of intussusception has not been done in Japan. Therefore, in this chapter, epidemiology of intussusception is discussed mainly based on the results of epidemiologic studies in foreign countries.

Incidence

CQ1: What is the incidence of intussusception in children and its trend over time?

A: The incidence of intussusception is approximately 50 per 100 000 infants younger than 1 year. There is no significant change of incidence over time in Japan, but the incidence rates are reported to be declining in some foreign countries in 10-year strata.

There are no national statistics regarding the incidence of intussusception in Japan. There are, however, a few reports on the incidence of intussusception in local areas, which showed conflicting results and no significant trend over time.5,6

In New York states, a large-scale study7 on the incidence of intussusception in children younger than 1 year old was carried out by reviewing hospital discharge data from 1989 to 1998. The average annual incidence of intussusception was 5.4 cases per 10 000 infants, and the incidence declined from 6.1 to 3.9 per 10 000 during the decade (level 2b). In Denmark, a population-based cohort study8 of 1.7 million children younger than 5 years of age was conducted during 1980–2001. The 5-year cumulative incidence rate of intussusception was 17.2 cases per 10 000 person-years during 1980–1989, but declined to 7.1 cases per 10 000 person-years during 2000–2001, which is equivalent to a total reduction of the incidence rate of 55% during the 1990s compared to the 1980s (level 2b). More recent 3-year surveillance (2003–2005) in Switzerland9 showed that the estimated annual incidence rate of intussusception in infants younger than 1 year old was 56 per 100 000 births on average (level 3b).

CQ2: What are the age distribution and sex ratio of intussusception in children?

A: The age distribution showed that more than half of intussusceptions occur in infants younger than 1 year old, and the incidence was rare in infants younger than 3 months old and in older children after 6 years of age. The male-to-female ratio was approximately 2:1.

A review of 14 Japanese papers showed that infants younger than 1 year old comprised 58.0% (48.8–68.5%) of 5279 intussusceptions in children,10 and patients aged more than 3 months and younger than 2 years corresponded to 89.2% of 877 children11 (level 4). The age distribution of all intussusception cases in a 3-year surveillance study in Switzerland9 also showed a very low occurrence rate of 1% for intussusceptions in children younger than 3 months old (level 4).

The review of the Japanese literature showed male predominance over female in the ratio of 2.05:1 (4607:2248).10 The male-to-female ratio of intussusception in three large-scale epidemiologic studies7–9 in foreign countries ranged from 1.6 to 2.1:1.

CQ3: Are there seasonal tendencies for intussusception?

A: There are annual fluctuations in occurrence of intussusception, but there is no seasonality.

There is a tendency for intussusception to occur in succession within a specific timeframe, but most literature denied seasonality in the rate of intussusception, as opposed to a peak occurrence of rotavirus gastroenteritis in winter7,9,12 (level 2b, 3b). The lack of seasonality may reflect influences of a variety of epidemic pathogens.

Causes

CQ4: What causes intussusception in children?

A: There are idiopathic intussusceptions without an identifiable cause and secondary intussusceptions due to a distinct pathological lead point (PLP) or underlying abnormality.

The majority of cases are idiopathic ileocolic intussusceptions without obvious cause other than lymphoid hyperplasia of the terminal ileum. On the other hand, PLP were seen in 3.9% (80 PLP out of 2069 intussusceptions) in the review of the Japanese literature.10 Reviewing the Japanese literature, Hoshino et al.13 reported that in 176 cases, the most common focal lesions included (in decreasing order of incidence) Meckel diverticulum (32.4%), duplication cyst (12.5%), aberrant tissue (8.5%), intestinal polyp (8.5%), lymphoma (5.7%), and Henoch–Schönlein purpura (3.4%) (level 4). The frequencies of PLP in this review were almost the same as those reported by Navaro and Daneman14 (level 4).

Common findings preceding idiopathic intussusceptions include upper respiratory tract infection or enterocolitis. Adenovirus infection was detected in 20–44% of these patients15–18 (level 3b). Rotavirus has been also implicated as the cause of intussusceptions, but currently this association is disputed in many reports7–9,12 (level 2b, 3b).

CQ5: Is the incidence of a pathologic lead point (PLP) higher in older children?

A: The incidence of secondary intussusception due to a PLP is approximately 5% in children younger than 1 year, and is progressively more likely with advancing age. Approximately 60% of intussusceptions in children over the age of 5 years old have PLP.

Blakelock and Beasley19 reported that the percentage of intussusceptions due to PLP increased with the patient's age, from 5% in infants younger than 1 year of age to 60% in older children over 5 years of age (level 5); however, in terms of the absolute number of intussusceptions due to PLP, 44% were in the age group younger than 5 years of age20 (level 4).

Recurrence rate

CQ6: What is the recurrence rate of intussusception?

A: The recurrence rate of intussusception as a whole is on average 10%, and the recurrence rate after surgical reduction is lower at approximately 4%.

In a review of nine Japanese papers, the overall recurrence rate of intussusception after enema reduction was an average of 10.3% (392 recurrences out of 3817 intussusceptions10). In the foreign literature, recurrence rates after enema reduction were also on average 10% in the range of 9–12%, regardless of air versus liquid enema technique21–23 (level 4).

On the other hand, the recurrence rate after surgical reduction was reported as lower than 4%21,24,25 (level 4).

Death

CQ7: How many annual intussusception-associated deaths are reported in Japan and what is the mortality rate?

A: There are autopsy reports of intussusception-associated deaths every year, but there are no accurate statistics on the number of deaths and the mortality rate in Japan.

Mortality from intussusception is considered very rare in Japan, but there were 51 intussusception-associated autopsies of children younger than 14 years old reported to the registry of the Japan Pathology Association between 1989 and 2008.26 Forty of these deaths were infants younger than 1 year old. This is an average of at least 2.6 child or 2.0 infant deaths annually in Japan (Fig. 2). There are also reports of forensic autopsy cases in which only non-specific or minor manifestations were observed until abrupt deterioration occurred27–29 (level 4).

Figure 2.

Intussusception-associated autopsies of children younger than 14 years old in Japan. inline image, 2–14 years old; inline image, 0–1 year old.

Diagnosis

Deaths from intussusception are avoidable if the diagnosis is made promptly and treatment is initiated appropriately. Most intussusceptions can be reduced successfully without operation. The purpose of this section is to guide clinicians in diagnosing intussusceptions at an early stage and to protect children from bowel necrosis and death.

Need for standardized diagnostic criteria

CQ8: What are the diagnostic criteria for intussusception?

A: There are no clinical diagnostic criteria for intussusception neither in nor out of the country. Therefore the guideline committee proposes the following diagnostic criteria aimed at an early diagnosis (Table 3).

Table 3. Diagnostic criteria for intussusception in children (A proposal)
Criteria A
 Abdominal pain or irritability
 Bloody stool (including blood detected by enema)
 Abdominal mass or distension
Criteria B
 Vomiting
 Pallor
 Lethargy
 Shock
 Abnormal bowel gas pattern on plain abdominal radiograph
Criteria C
 Characteristic image of intussusception by contrast enema, ultrasound, computed tomography or magnetic resonance imaging
 “Suspicious diagnosis” is defined as when any of the following criteria are met:
 One criterion A (abdominal pain or irritability) when it is intermittent
 Two criteria A
 One criterion A plus one criterion B
 Three criteria B
 “Definitive diagnosis”:“Suspicious diagnosis” plus one of the criteria C

The classic triad of abdominal pain, vomiting, and bloody stool were manifested in only 21–36% of cases at presentation30–32 (level 4). In general, the earlier a child visits a clinic, the lesser the degree or severity of the symptoms. These diagnostic criteria were aimed at early detection of the condition and prompt initiation of the treatment. Criteria A consist of the three most specific symptoms and signs, and criteria B consist of less specific symptoms and signs. Definitive diagnosis is defined as characteristic findings of intussusception by imaging (criteria C). These diagnostic criteria are modifications of the case definition developed by the Brighton Collaboration Intussusception Working Group to investigate the association between vaccination and intussusception33 (level 2b).

Clinical context and clinical manifestations

CQ9: When do we suspect intussusceptions?

A: If we include irritability and crying of unknown origin in infants in abdominal pain, abdominal pain is the most common clinical presentation, which is usually followed by refractory vomiting. Intussusception should be suspected at this early stage (recommendation A).

Abdominal pain, including irritability, is the most frequent presenting symptom of intussusception.30–32 Pain is described as intermittent and crampy. Vomiting that is refractory at the beginning and later becomes bilious is the second most frequent sign30–32 (level 4). Bloody stools were detectable only in 16% of cases with duration of symptoms less than 12 h, and rectal bleeding was the primary sign in only 8% of cases30 (level 4). Clinicians must also suspect intussusceptions in cases in which lethargy or septic shock is the first presenting symptom21,34 (level 4).

CQ10: What are the characteristics of the clinical course of intussusceptions?

A: Intussusception presents with abdominal pain followed by vomiting. Bloody stool is characteristic to intussusception, but the incidence of bloody stool is low initially and later becomes higher with time elapse.

Much of the literature shows that abdominal pain, vomiting, and bloody stools appear in this order.

Vomiting has a high incidence next to abdominal pain30–32 (level 4). Bloody stool is characteristic to intussusception, but is a late finding.30,31 The presence of the classic triad generally is associated with long-standing duration of symptoms.30,31 Abdominal distension and fever occur more frequently in cases after 24 h from the onset.32 As a late sign, some infants present with profound listlessness and apathy34 (level 4).

CQ11: Is the diagnostic enema useful?

A: Confirmation of macroscopic bloody stools or occult blood by enema or rectal examination is helpful for diagnosis, when clinical symptoms are obscure (recommendation B).

Spontaneous passage of bloody stools is not commonly present at the initial stage of intussusceptions. Therefore diagnostic enema is helpful when intussusception is suspected. The presence of blood in stools increased from 40% to 97%35 after diagnostic enema and from 53% to 71% by testing stools obtained by rectal examination for occult blood36 (level 3b, 4); however negative bloody stools do not necessarily rule out the possibility of intussusception.

CQ12: What is the pathophysiological mechanism of bloody stools?

A: The pathophysiologic mechanism of intussusception is strangulating obstruction. Impaired venous return and ischemia of the invaginated bowel lead to hemorrhage from the bowel wall.

Invagination of the bowel is accompanied by dragging the mesenteric vessels into the intussusceptum. Compression and angulation of arteries and veins cause ischemia and congestion of the bowel wall37 (level 5), resulting in mucosal edema and hemorrhage. At this late stage of strangulation, stool becomes bloody and mixed with mucus. After this stage, ischemia advances to transmural necrosis and eventually perforation occurs.

CQ13: What are the characteristic physical findings of the abdomen?

A: A sausage-shaped mass is palpated in the right hypochondrium. The incidence of a “Dance sign,” emptiness of the right lower quadrant, is low. Abdominal distension increases with time. Palpation of the abdomen is highly recommended (recommendation A).

Typically, a tender “sausage-shaped” mass in the right upper quadrant of the abdomen is palpable in 30–85% of cases,21,30–32,35 depending upon the skill of the clinician (level 4). Emptiness of the ileocecal region (Dance sign) was observed in only 5% of cases, and was not diagnostic30 (level 4). Abdominal distention appears at high frequency as a late sign after 24 h duration32 (level 3b).

Laboratory data

CQ14: Are blood tests necessary for diagnosis of intussusception?

A: Blood tests do not have a diagnostic value for intussusception, but they are useful to evaluate the general condition of the patients (recommendation B).

There is no specific finding in blood tests to diagnose intussusception; however, if a patient is in severe condition due to bowel necrosis, leukocytosis is seen38 (level 3b). If the duration of symptoms is long, metabolic acidosis is expected. There is one report demonstrating that plasma C-reactive protein (CRP) was a useful marker to predict the clinical outcome of intussusception39 (level 3b).

Imaging

CQ15: Are plain abdominal radiographs necessary for diagnosis of intussusception?

A: Plain abdominal radiographs have a limited diagnostic value, but they are useful to detect free peritoneal air or small bowel obstruction (recommendation B).

Abdominal radiographs are often unhelpful in diagnosing intussusception. Sargent et al.40 reported limited agreement between three observers of radiographs and the diagnostic accuracy of abdominal radiographs was only 40%, including equivocals (level 3b). The best positive predictors of intussusception were opacity of soft tissue mass along the course of the colon and sparse large bowel gas in the right iliac fossa40 (level 3b). Lee et al.41 reported radiolucencies in the soft tissue mass (crescent and target lucencies) as characteristic signs of intussusception on radiographs (level 3b). An ileocolic intussusception can be excluded by the presence of gas and feces in the cecum. Small bowel obstruction is a late sign and free peritoneal air is a contraindication of enema reduction42 (level 5).

CQ16: What is the role of sonography in diagnosis of intussusception?

A: Sonography has nearly 100% sensitivity and specificity in diagnosis of intussusception, and is useful for screening the condition (recommendation A).

Sonography is used as the modality of choice for screening intussusception at many institutions. It has great merit in that it requires no radiation. It has high sensitivity of almost 100% and specificity of 88–100%43–45 (level 1c). It also has the benefits of high ability to detect PLP. Intussusception can usually be found with sonography on the right side of the abdomen as a “target,”44“doughnut,”44 or “crescent-in-doughnut”46 sign in the transverse plane, and as “pseudokidney” sign44 on longitudinal section (level 3b).

Occasional false-positive examination includes any cause of bowel wall thickening, such as enterocolitis and hematoma. Therefore, scanning of both the transverse and the longitudinal plane is important for the diagnosis of intussusception.43,45 Sonography is sometimes useful for finding other intra-abdominal diseases in children with suspected intussusceptions in whom no intussusception is found. The spontaneous reduction of intussusception, which is usually limited to the small bowel, has been frequently appreciated on sonography47 (level 4).

CQ17: Is contrast enema necessary for diagnosis of intussusception?

A: Sonography has priority for diagnosis, but if the diagnosis is uncertain, or when sonographic expertise is not available in an emergency situation, contrast enema study is necessary (recommendation A).

Contrast enema has several merits, although it has the disadvantage of radiation exposure. The technique of contrast enema is easy to learn, well-known to almost all clinicians, and is less likely to miss the diagnosis of intussusception than sonography. Once the diagnosis of intussusception is made, the clinician can proceed to the reduction with the same modality.42 The disadvantage of sonography is that the accuracy of diagnosis depends on the experience of the operators, who may have insufficient training. If one does not have confidence in utilizing sonography, or sonography is not available in an emergency situation, contrast study is helpful to confirm the diagnosis48 (level 5).

CQ18: Is computed tomography (CT) useful for diagnosis of intussusception?

A: Considering radiation exposure, CT is not the first choice for diagnosis of intussusception. But it is useful when intussusception cannot be ruled out, or in rare cases of small-bowel intussusception (recommendation B).

CT scan has high resolution in the diagnosis of intussusceptions, but it is not practically used because of the larger dose of radiation required and the necessity for sedation. The use of CT should be reserved for delineation of small-bowel intussusception and/or a PLP in older children with atypical symptoms49 (level 4).

Severity assessment

Intussusception is a strangulation obstruction, leading to bowel ischemia, necrosis, sepsis, and eventually death. There are a variety of degrees of severity from mild to severe in the pathophysiology of intussusception. The aim of the severity assessment is to select the appropriate procedures for diagnosis, treatment, or prompt referral to a tertiary hospital according to the severity of the intussusception.

Severity assessment criteria

CQ19: What are the severity assessment criteria for intussusception in children?

A: There is no report on severity assessment criteria for intussusception in children. Therefore the guideline committee proposes the following severity assessment criteria (Table 4).

Table 4. Severity assessment criteria for intussusception in children (a proposal)
SeverePoor general condition or one of the following conditions indicating bowel necrosis
1) Septic shock
2) Peritonitis
3) Free peritoneal air on a plain abdominal radiograph
ModerateStable general condition, but one of the following conditions indicating possible ischemia of the bowel
1) Duration of symptoms beyond 48 h
2) Infants of 3 months of age and younger
3) The apex located beyond the splenic flexure
4) Ileoileocolic type
5) White blood cells>20 000/µL, elevated CRP>10 mg/dL
6) Small bowel obstruction on a plain abdominal radiograph
7) Ultrasound findings of lack of blood flow, trapped fluid between intussuscepted bowl walls, and presence of pathological lead point
MildStable general condition in which criteria of “severe” or “moderate” are excluded.

“Severe” intussusception is a state of poor general condition from its basic disease or suspected bowel necrosis. After adequate resuscitation by intensive care, surgery is the treatment of choice. Contrast enema reduction is contraindicated, and sonography is preferable as a diagnostic modality.

“Moderate” intussusception is a state of stable general condition, but is accompanied by symptoms and signs of possible bowel ischemia. Enema reduction is not contraindicated but because of the possibility of perforation or unsuccessful reduction, cautious selections of contrast media, reducing pressure, reduction time, and reduction attempts are necessary.

“Mild” intussusception is a state which does not fulfill the conditions of “severe” or “moderate” intussusceptions.

These criteria were compiled on the basis of the evidence of CQ20–CQ26.

Clinical context and clinical manifestations

CQ20: Do clinical symptoms and physical findings correlate with severity of intussusception?

A: Shock, peritonitis, duration of symptoms, age, location of the apex, and invagination type do correlate with severity. Therefore, a detailed history of clinical symptoms and physical examination are important (recommendation A).

Severe dehydration, septic shock, and signs of peritonitis are suggestive of a “severe” state of intussusception. Shock and peritonitis are contraindications for enema reduction50,51 (level 3a).

Duration of symptoms of more than 48 h was significantly correlated with failure of enema reduction and with a high rate of bowel resection38 (level 3b). The longer the duration of symptoms, the lower the likelihood of successful enema reduction and the higher the rate of bowel perforation22 (level 3b); however, a long duration of symptoms itself is not a contraindication for attempted enema reduction.

For infants, age of 3 months and younger was associated with a low success rate of reduction,52 and younger age was a predictor of perforation22 (level 3b).

The location of the apex has also been correlated with severity. Reduction success rate was low when the intussusception was encountered beyond the splenic flexure53 (level 3b). Successful enema reduction is less likely, especially once the apex reaches the rectosigmoid region54 (level 3b).

Among types of intussusceptions, the ileoileocolic type is also significantly correlated with low enema reduction rate22,55 and bowel necrosis22 (level 3b).

Laboratory data

CQ21: Are laboratory data useful for severity assessment?

A: Leukocytosis of white blood cell counts>20 000/µL and elevated CRP>10 mg/dL are often observed in moderate to severe intussusceptions. White blood cell count and CRP are useful for severity assessment (recommendation B).

Leukocytosis is more frequently seen in moderate-to-severe cases. In one study, the incidence of white blood cell count greater than 20 000/µL was significantly higher in the bowel-resection group compared with those of the operative-reduction group and the enema-reduction group38 (level 3b).

Elevated CRP>10 mg/dL also reflects the degree of severity of the condition. The incidence of CRP>10 mg/dL was significantly higher in the bowel-resection group compared with those of the operative-reduction group and the enema-reduction group39 (level 3b).

Imaging

CQ22: Are plain abdominal radiographs useful for severity assessment?

A: Free peritoneal air and small bowel obstruction on plain abdominal radiographs are useful for severity assessment (recommendation B).

Free intraperitoneal air is said to be a contraindication for enema reduction, but there were no relevant cases documented in the literature after 1966. The presence of small-bowel obstruction is a risk factor for failure of enema reduction and for bowel resection56 (level 3b), but it is not a contraindication to performing the enema.

CQ23: Is sonography useful for severity assessment?

A: Lack of blood flow, trapped fluid between intussuscepted bowl walls, and presence of PLP correlate with severity of intussusception. Sonography is useful for severity assessment (recommendation B).

Color Doppler sonography is useful in predicting the degree of bowel ischemia. Absence of flow in the intussusception has been shown to be predictive of bowel necrosis and the need for bowel resection57–59 (level 3b). Detection of blood flow was associated with successful enema reduction, and lack of flow is suggestive of failure of enema reduction58,60,61 (level 3b).

Non-visualization of blood flow by color Doppler sonography was not a contraindication for attempted air enema reduction, however.60 These different results may be influenced by the ability of the equipment used and the technique of the examiners.

Trapped peritoneal fluid between two limbs of the intussusceptum was also shown to be associated with a significantly lower reduction success rate and higher degree of bowel ischemia62,63 (level 3b). Although trapped fluid is not a contraindication for attempting air enema reduction, vigorous, high-pressure enema reduction should not be attempted.62

The presence of free intraperitoneal fluid in small or moderate amount does not predict a lower enema success rate, but a large amount of intraperitoneal fluid is predictive of surgery43,45 (level 3b).

The presence of a PLP is a risk factor for irreducible intussusception and surgery31,53,64 (level 3b), but it does not necessarily mean that enema reduction is impossible.45

CQ24: Is contrast enema useful for severity assessment?

A: Location of the apex and invagination type correlate with severity of intussusception. Contrast enema is useful for severity assessment (recommendation B).

Location of the apex and invagination type demonstrated by contrast enema correlate with severity of intussusception (See CQ20). There are few studies that have discussed correlation between contrast image and severity. Dissection sign in intussusceptions is reported to have correlation with a failed enema reduction56 and bowel necrosis65 (level 3b).

CQ25: Is CT study useful for severity assessment?

A: There are a few case reports on CT findings demonstrating bowel necrosis; however, evidence levels are low and moreover there is a concern of radiation exposure in CT. CT is not useful for severity assessment (recommendation C2).

There are no reports demonstrating a sufficient evidence level that discuss the correlation between CT findings and the severity of the intussusception. Sonography has priority in the assessment of severity. The use of CT should be reserved for special cases, in which sonography is of no use (CQ18).

Prognostic factors

CQ26: Is it possible to predict bowel necrosis?

A: Poor general condition suggests bowel necrosis. Duration of symptoms beyond 48 h, ileoileocolic type, and lack of blood flow by color Doppler are valuable indicators to predict bowel necrosis.

Poor general condition suggests gangrenous intussusceptions. As predictors of bowel necrosis, duration of symptoms beyond 48 h, ileoileocolic type, and lack of blood flow by color Doppler have been considered in previous clinical discussions. None of these features, in isolation, is an absolute contraindication to enema reduction; however, a combination of these factors will significantly increase the risk of bowel necrosis, the possibility of bowel resection, and incidence of complications.

Criteria for patient transfer

CQ27: What are the criteria for patient transfer?

A: Patients with severe intussusception should not undergo enema reduction, but should be transferred immediately to a tertiary hospital where intensive care, including surgery, is possible (recommendation A).

Patients with moderate intussusceptions need careful attempt at enema reduction. If the attempt is in failure, the patient should be transferred to surgical facilities as soon as possible (recommendation A).

Patients with mild intussusception are good candidates for enema reduction. If the reduction fails, the patient should be transferred to surgical facilities as soon as possible (recommendation A).

Severely ill patients with peritonitis or in shock are contraindicated for enema reduction, and it is recommended to transfer these patients immediately to tertiary hospitals, including children's hospitals, where intensive preoperative care is possible and surgeons (ideally pediatric surgeons) are available. Enema reduction rate was higher, and hospital stay was shorter when patients were treated at children's hospitals in comparison with those treated at non-children's hospitals, owing to a positive volume-outcomes correlation66,67 (level 2b).

If an attempted enema reduction is a failure in mild-to-moderate cases, it is also necessary to refer these patients to a hospital where surgeons are available. Prompt transfer of patients is important for improvement in case management. Delay of transfer of more than 24 h from a non-teaching hospital to a teaching hospital increased the incidence of operation significantly66,68 (level 2b).

Treatment

It is now generally accepted that non-operative reduction should be attempted in most patients with acute idiopathic intussusception. Based on the reduction success rates published in the recent literature, one could aim to achieve at least an 80% success rate, or even as high as 95% (See CQ38); however, these rates will be influenced by the specific patient population one sees.

Fluid

CQ28: Is intravenous fluid necessary in patients with intussusceptions?

A: In cases of severe and moderate intussusceptions, circulatory insufficiency and dehydration should be treated with extracellular fluid replacement (recommendation A).

In cases of mild dehydration, intravenous fluid is not necessarily required, but it is desirable to maintain the venous route to handle complications expected by enema reduction (recommendation B).

In cases deemed moderate-to-severe by severity assessment, it is important to correct the child's hypovolemia and dehydration with adequate intravenous fluid replacement prior to surgery or enema reduction50,69 (level 2c, 3a). Dehydration is observed in about 50% of cases of intussusception69 (level 2c).

In mild cases with good hydration, intravenous resuscitation is not necessary; however, placement of an IV-line is desired for safety to cope with complications that may arise during enema reduction.

Anesthesia

CQ29: Is general anesthesia necessary for enema reduction?

A: There is no significant difference between enema reductions with and without general anesthesia. General anesthesia is not necessary for reduction (recommendation C2).

Some authors in the past have recommended routine use of general anesthesia, including gas,70 thiopenthal,71 and ketamine,72 which they believed improved enema reduction rate (level 4); however no differences have been demonstrated in reduction rates between two groups with and without anesthesia73 (level 3b). On the contrary, in an animal experiment, pig groups in which straining (Valsalva maneuver) was lost under deep general anesthesia showed a higher colonic perforation rate by enema reduction when compared with the group in which straining was preserved by light anesthesia74 (level 5).

There are also papers recommending the use of general anesthesia in the second attempt in the operating room with improvement of reduction rates75,76 (level 3b, 4); however, in these cases, improvement of reduction rates may possibly be attributed to the effect of delayed repeated enema (see CQ42), not of general anesthesia.

CQ30: Is epidural anesthesia necessary for enema reduction?

A: There is little evidence that epidural anesthesia or saddle block improves reduction rate by enema. Epidural anesthesia is not necessary for reduction (recommendation C2).

There are reports in which intussusceptions were reduced under epidural anesthesia77 or saddle block78 after a failed attempt at enema reduction (level 4). These reports were not controlled studies with comparison groups. There is a possibility that, in these cases, intussusception was reduced also by delayed repeat enema as described in CQ42.

Sedation

CQ31: Is the use of sedation effective for enema reduction?

A: There are few papers discussing the effectiveness of sedation. The use of sedation is left to the physician's preference (recommendation C1).

Various kinds of sedation, such as diazepam,72,76,79 chloral hydrate,76 pentazocine,80 meperidine,81 morphine sulfate,82 etc. have been customarily used (level 4). There is a comparative study of analgesic premedication, which improved the reduction rate81 (level 3b); however the conclusion of this study is questionable, because the reduction rate of the sedation group was 68%, while that of the non-sedation group was only 36%, which is extremely low. Therefore, there is little evidence to support or condemn the use of sedation. The use of sedation depends on the clinician's preference at present.

Antispasmodics

CQ32: Is the use of butylscopolamine (Buscopan) effective for enema reduction?

A: There is no comparative study on the effectiveness of Buscopan in enema reduction. The use of Buscopan is left to the physician's preference (recommendation C1).

Buscopan has been used customarily as an antispasmodic agent, to irrigate the colon smoothly with contrast media79,83 (level 4); however, there are no controlled studies evaluating its effectiveness. The use of Buscopan is left to the clinician's preference at present.

CQ33: Is the use of glucagon effective for enema reduction?

A: The effectiveness of glucagon in the improvement of reduction rate is inconsistent. Glucagon is not recommended for reduction (recommendation C2).

Glucagon has muscle relaxant effects as well as Buscopan, and has been used for enema reduction. In earlier reports, the reduction rate was higher when Glucagon was used80,82 (level 3b); however, more recent randomized controlled studies have shown that glucagon is of no benefit84,85 (level 2b). The use of glucagon is not recommended as it is an expensive drug in comparison to Buscopan, and health insurance in Japan may not cover the fee.

Imaging

CQ34: Which is selected for enema reduction, fluoroscopy or sonography?

A: There is no comparative study on reduction rates by fluoroscopy versus sonography. The use of sonography has the advantage of eliminating radiation exposure; however, considering the differences in medical equipment and expertise of physicians at present, the choice depends on the clinician's preference.

There are many reports of enema reduction under sonography76,86–97 since Bolia's report98 in 1985. The greatest advantage of sonography is that it does not involve radiation exposure to children, and therefore reduction can be attempted repeatedly without concern for time76 (level 4).

The modality of sonography has another advantage in that it is able to detect PLP on reduction, such as Meckel diverticulum or duplication cysts20,99 (level 4, 5). The main disadvantage of sonography is the need for training of a clinician, because it is an extremely operator-dependent modality89,99 (level 5).

There is no study on the direct comparison of reduction with fluoroscopy versus reduction with sonography, but several reports on the use of sonography with either water or air reduction techniques have shown reduction rates higher than those using fluoroscopy76,89,91,95 (level 4). Considering the differences of medical environments and expertise of clinicians, the choice of either fluoroscopy or sonography depends on a clinician's preference.

Contrast media

CQ35: Which contrast media is selected for enema reduction under fluoroscopy?

A: Barium has traditionally been used as a contrast media, which most physicians are accustomed to; however, once perforation occurs during the enema, the patient becomes severely ill. Barium is no longer recommended (recommendation D).

Use of contrast media other than barium is recommended (See CQ36).

After Ravitch's report100 in 1948, the use of barium for enema reduction has become the definitive non-operative management throughout the world; however, the major disadvantage of barium enema reduction is the complication of barium peritonitis when perforation occurs during the enema101–105 (level 4, 5). Barium spilled into the abdominal cavity and mixed with feces cannot be removed completely. Barium adhered to the peritoneum and omentum remains radiologically for years and can cause intestinal obstruction later. Once perforation has occurred, patients with barium enema have been shown to require bowel resection more often, longer hospital stays, and increased morbidity rates compared to those with air103,106 or water-soluble contrast101,106 enema (level 3b, 5). Because of this risk, water-soluble iodinated contrast media is preferred over barium as an alternative contrast media for enema reduction77,104,106–108 (level 4, 5).

There is no direct comparison of reduction rates between the use of barium enema and water-soluble iodinated contrast enema under fluoroscopy, but reduction rates using barium enema in the Japanese literature are 87–95%,73,77,78,80 which is comparable with reduction rates of water-soluble iodinated contrast enema61,108,109 (level 4). There have been reports of comparison of reduction rates between the use of barium and air under fluoroscopy in the foreign literature. These foreign studies have shown that the reduction rates using barium are lower than those using gas or air (53–85% vs 75–100%110–113) (level 3b) (See CQ38).

The advantage89 of the use of the barium enema reduction technique has been claimed to be its clear delineation of the reducing process of intussusception, but water-soluble agents diluted to iso-osmolar concentrations still allow appropriate anatomical delineation under fluoroscopy104,108 (level 4). Water-soluble iodinated contrast media is recommended instead of barium if one chooses hydrostatic reduction under fluoroscopic guidance.

CQ36: Which contrast media is appropriate for enema reduction under fluoroscopy, air, or liquid?

A: In contrast to Europe and North America, where air is replacing barium for reduction, either diluted Gastrografin (diatrizoate meglumine) or air is chosen in Japanese institutions. The reduction rates of these two contrast media are comparable, leaving the selection to the clinician's preference.

Surveys112–116 of pediatric radiology departments in North America and Europe have shown a trend among pediatric radiologists to change from hydrostatic reduction to pneumatic reduction techniques (level 5). In Japan there are two flows of shift, one to water-soluble iodinated contrast media and the other to air.

Air and liquid contrast media (barium) were compared in a controlled, randomized trial by Meyer et al.113 This study showed no significant difference of reduction rates between two the groups, but air enema has the advantage of rapid reduction and less radiation exposure (level 2c). A disadvantage of the air enema technique under fluoroscopy is that the delineation of the intussusception image is less clear, and clinicians who are accustomed to positive contrast media may need to get used to it. It may be especially more difficult to visualize both the intussusception and reduction in patients with marked amounts of gas in the small bowel.72

For air reduction, pressure needs to be carefully monitored by pressure gauge,90 which may require a pressure release device and an experienced operator. Once perforation occurs, an emergent tap of the peritoneal cavity by an 18-gauge needle is necessary for tension pneumoperitoneum69,90,103 (level 4).

There are case reports of patients for whom there was passage of air into the terminal ileum without complete reduction of the ileocolic intussusception117,118 (level 4). These cases can be erroneously interpreted as a successful reduction.

CQ37: What media is appropriate for enema reduction under sonography?

A: There is no significant difference of reduction rates between air and physiological saline water. Either of them can be used according to the preference of the physician.

There are several series studies that have achieved equally high reduction rates using air91,93,95,96 or liquid76,86–89,92,94 reduction under sonographic guidance (level 4), but no comparative study of air and liquid has been carried out. Overall, there is more collective experience using liquid enema reduction than using air. The preference of liquid over air may be due to its clearer contrast to pre-existing small intestinal gas at the intussuscepted region. For liquid contrast, normal saline is commonly used76,92 (level 4).

Pressure

CQ38: What is the proper pressure for reducing intussusceptions?

A: Liquid enema using diluted Gastrografin is started with caution at a pressure of 100 cmH2O and gradually increased to a maximum limit of 120 cmH2O (equivalent to 94 mmHg). With gas reduction, gas is inflated into the rectum at the initial pressure of 80 mmHg which may be increased up to 120 mmHg. In infants younger than 6 months of age who have a higher risk of perforation, the starting pressure of liquid and gas enemas should be 80 cmH2O and 60 mmHg, respectively, and great attention should be paid to the increase of pressure (See CQ41) (recommendation B).

Notwithstanding, there is always a risk of perforation.

Studies on reduction pressure are accumulated mainly based on barium reduction. The “Rules of Threes” (three attempts of 3 min each, with enema bag 91 cm (3 feet) above the fluoroscopy table) have been advocated119 (level 4), and seem to have been adhered to strictly by pediatric radiologists overseas in the past. This relatively low reduction pressure may explain low reduction rates reported in the foreign literature in comparison with those reported in the Japanese literature. Higher pressure has been applied in reduction in attendance of surgeons as well as pediatricians in Japan.

Liquid enema reduction under fluoroscopy and normal saline enema reduction under sonography

Traditional practice dictates a barium column of 100 cm to a maximum of 120 cm if the intussusception is static75,109,120 (level 4). One should be cautious that the pressure is different depending on the type of liquid and its dilution, even if the height of the column is the same. Success rates with hydrostatic reduction except for barium enema have varied from 71 to 98%75,76,89,92,94,109,120 (level 4), reflecting local referral patterns, selection criteria, and the skill of operators.

Air enema reduction under fluoroscopy and sonography

Air is carefully pumped into the rectum up to a pressure of 80 mmHg at first, which is equivalent to 91 cm in barium reduction110,111 (level 4). The pressure may be increased to 100 mmHg and to a maximum limit of 120 mmHg69,71,72,90,91,93,95,96 (level 4), which is much higher than the maximum limit of liquid enema reduction. Success rates with air enema reduction have varied from 73 to 97%69,71,72,90,91,93,95,96,105,110 (level 4), which is not necessarily higher than the reduction rate of liquid reduction. Air enema is preferred overseas, because it is considered cleaner, cheaper, and safer when perforation occurrs.106 Guo et al.90 stated that the maximum pressure in young infants should be limited to 80 mmHg (level 4).

The correlation between maximum-reduction pressure and reduction success rate in three different contrast media, including the Japanese literature,121 is illustrated in Figure 3.

Figure 3.

Correlation between maximum reduction pressure and reduction success rate in different contrast media121 (● Barium, ▴ Air, ○ Water-soluble contrast).

CQ39: How many attempts are appropriate for enema reduction, and for what duration?

A: “Three attempts of 3 min” is the standard (recommendation A).

The limits do not need to be strictly applied in reduction under sonography, as radiation exposure is not a problem.

There is little evidence supporting the commonly taught “Rules of Threes” regarding the liquid enema technique, particularly in regards to the appropriate height of the enema bag. There are reports of more than three attempts,70,109 or 5 min duration70,72,75 (level 4); however, there is no doubt that radiation times should be kept to a minimum. Therefore, three attempts of 3 min duration is the ideal standard.

On the other hand, sonography does not involve radiation exposure to children, and therefore reduction can be attempted repeatedly without concern for time76,89,93 (level 4).

Complications

CQ40: What is the incidence of bowel perforation in enema reduction?

A: Perforation rates differ depending on contrast media. The perforation rate with barium is the lowest at 0.14%, perhaps because the reduction pressure is set low for safety. The perforation rate with liquid is 0.37%. Whereas, the perforation rate with air tends to be higher, with a rate of 0.76% possibly due to higher reduction pressure.

The most important potential complication of enema is bowel perforation. In multiple reviews, perforation rates for air versus liquid enema are reported not to be significantly different. But there are many reports of high perforation rates by air enema. For example, Stein et al.22 reported a high perforation rate of 2.8% with air enema (level 4); however, Guo et al.90 reported a very low perforation rate with air enema of 0.141% in 6396 intussusceptions (level 4). Accordingly, the overall mean perforation rate of air enema became extremely low in previous reviews. But this report was not included in our analysis, because of equivocal data as to the number of subjects. As the results show, perforation rates differed depending on contrast media121 (Table 5). Perforation with barium was the lowest at 0.14%, perhaps because the reduction pressure is set low for safety. The perforation rate with liquid was 0.37%. Whereas, perforation rate with air was the highest at 0.76%, possibly due to higher reduction pressure.

Table 5. Reduction rates and perforation rates in enema reduction121
Contrast mediaOverall reduction (reduction rate %)Perforation (%)Overall perforations (perforation rate %)
  • *

    Water-soluble contrast other than barium.

Barium6365/8406 (75.7%)0–2.5412/8406 (0.14%)
Liquid*2013/2409 (83.6%)0–3.309/2409 (0.37%)
Air6519/8047 (81.0%)0–5.9861/8047 (0.76%)

CQ41: In which cases does bowel perforation tend to occur?

A: Risk of perforation is high in infants younger than 6 months of age and with the use of high pressures at attempted reduction.

Perforation occurs during enema reduction in ischemic areas of the colonic intussuscipiens or necrotic areas in the outer layer of the intussusceptum122 (level 4). The most common site is at or just proximal to the intussusception in the transverse colon.

It is clear that the use of excessive pressure or an abrupt change of pressure during enema reduction is the main cause of perforation103 (level 4); however, perforation does occur at pressures even as low as 60–80 mmHg103,121 (level 4) (Fig. 4).

Figure 4.

Correlation between reduction pressure and perforations.121inline image, barium; inline image, air; inline image, gastrografin.

The statistical analysis of perforation shows that more than half of perforations occur in infants less than 6 months of age121 (Fig. 5). Particular care regarding enema reduction should be taken in younger children with a longer duration of symptoms or with evidence of small bowel obstruction on plain radiography22,122 (level 3b).

Figure 5.

Correlation between age and perforations.121inline image, barium; inline image, air; inline image, gastrografin.

An overly aggressive approach must be condemned in cases with risk factors122 (level 4).

Delayed repeat enema

CQ42: Does delayed repeat enema (DRE) improve the reduction success rate?

A: DRE improves reduction success rate. It is useful to attempt DRE, if the initial enema partially reduced the intussusception and if the patient is in a stable condition (recommendation B).

Operative reduction is the standard treatment after the failure of enema reduction of intussusceptions; however, 10–14% of intussusceptions have been found to be spontaneously reduced at operation123,124 (level 4). Hence, enema reduction was repeated at a certain time interval after the first failed attempt. Reduction success rates were improved by 50–85% in DRE cases with failed initial enema reduction61,75,125–128 (level 3b, 4).

The indications for DRE are clinically stable infants with no evidence of peritonitis and only when the initial enema achieved a partial reduction.125,128,129 It is believed that partial reduction and the time interval between attempts allow the venous congestion and edema of the bowel wall to decrease and facilitate the reduction of the residual bowel.75,125 Optimal timing for the repeat attempt has not been established, but a 30-min to 4-h delay after the initial attempt seems to be common125–129 (level 4).

Delayed enema should not be performed if the child is clinically unstable or if the initial enema failed to move the intussusception at all50,125,129 (level 4).

Admission

CQ43: Is it necessary to admit patients after enema reduction?

A: It is allowable to let the patient go home after an appropriate time of observation at an outpatient clinic or emergency room, when the patient is in a stable condition and has good access to medical facilities (recommendation C1).

Observation under admission is the standard care after a successful enema reduction in Japan. One has to be especially careful in regards to recurrence, because 40% of recurrences take place within 48 h of the primary reduction of intussusception130 (level 4); however, there are several reports from foreign countries in which uncomplicated patients with good hydration, no underlying diseases, and good access to hospitals are able to go home after observation at the outpatient clinic or emergency room131–133 (level 3b). Recurrence of intussusception outside the hospital did not affect clinical outcomes132,133 (level 3b).

Antimicrobial therapy

CQ44: Is it necessary to administer antimicrobial drugs after successful enema reduction?

A: Routine administration of antimicrobial drugs is not necessary after enema reduction (recommendation C1).

Serial blood culture studies both pre-enema and post-enema did not justify routine administration of antibiotics after enema reduction134 (level 3b). Antibiotics are not routinely used at most institutions115,135 (level 5). Antimicrobial therapy is justified only in the presence of an underlying sepsis.

Confirmation

CQ45: How is complete reduction by enema confirmed?

A: Sonography is the most effective method to confirm complete reduction and to exclude residual intussusception or recurrence (recommendation B).

Reduction is deemed to be satisfactory only if there is free reflux of contrast media into the distal small bowel loops without filling defect under fluoroscopy, together with resolution of symptoms and signs in the patients88 (level 4).

The same thing can be true for air enema or liquid enema under sonography.136 Sonography is useful to confirm complete reduction repeatedly in uncertain cases without free reflux of contrast media or with persistent filling defect of possible edema, suspected residual bowel or PLP43,45,50,136 (level 4). Edema of the ileocecal valves remains after successful reduction as a post-reduction “donut sign,” which is smaller than the target sign and not multi-concentric as is the target sign137 (level 3b).

CQ46: How should pathological lead points (PLP) be evaluated in recurrent or repeated cases?

A: In repeated episodes of more than twice or in older children, there is a higher risk of PLP. Sonography on enema reduction is the most helpful method to detect PLP (recommendation C1).

The incidence of PLP in all children with intussusceptions was 3.9% in the Japanese literature121 (See CQ4). Daneman et al.23 found that PLP were present in 14% of the children who had two or more recurrences compared to 4% of those children who had only one recurrence (level 3b). More than two recurrences after the initial enema reduction is the predictor of the presence of a PLP.

The age of the patient may be considered a predictor of the presence of PLP, particularly when the intussusception occurs in children older than 4–5 years of age20,138 (level 4), or in recurrent cases in children older than 2 years of age139 (level 4). Lymphoma patients who presented with intussusception ranged in age from 3 to 19 years (median 10 years)140 (level 4).

Small intestinal intussusception due to PLP has a high incidence in Peutz–Jeghers syndrome and Henoch–Schönlein purpura20,99 (level 4).

Sonographic findings are of particular value in identifying the rare instances of reduced PLP.20

Two-thirds of PLP were identified at ultrasound and 40% of PLP were diagnosed on liquid enema, while air enema had a lower rate of detection of 11%20 (level 4). CT is indicated when sonography fails to identify a suspected PLP20 (level 4).

Surgical treatment

CQ47: What is the indication for operation?

A: Operation is indicated in uncorrectable shock, suspect of bowel necrosis/perforation, peritonitis, irreducible intussusceptions, and the presence of PLP (recommendation A).

It is important to distinguish between indication and contraindication of enema reduction. Children with evidence of peritonitis, sepsis, or free air on abdominal radiographs are not candidates for enema reduction37,50,141 (level 5). These children should be stabilized first and then treated surgically. Operative treatment is also indicated when enema reduction has failed and a PLP was demonstrated or when a PLP is suspected in cases of multiple recurrence37,141 (level 5); however, multiple recurrences are not a contraindication to attempt enema reduction.

Non-operative reduction is not expected to be successful in intussusceptions limited to the small bowel.

CQ48: What is the indication for bowel resection?

A: Bowel resection is indicated in the presence of bowel necrosis/perforation, PLP, and operatively irreducible intussusceptions (recommendation A).

Indications for bowel resection are perforation of the bowel, necrotic bowel, possibly irreversible ischemia of the bowel, presence of a PLP, and operatively irreducible bowel37,141 (level 5). Practically, there may be occasions when it is difficult to judge whether the ischemia of the bowel is reversible or not. If there is doubt in regards to the reversibility of the bowel ischemia, it may be safer to resect the bowel and anastomose end-to-end.

CQ49: Are additional procedures effective to prevent recurrences?

A: There is no evidence to support additional procedures of ileopexy, severance of ileocecal band, or appendectomy to prevent recurrences (recommendation C2).

Highly mobile cecum has been implicated in the pathogenesis of intussusceptions. Therefore, many surgeons have performed severance of the ileocecal band, suturing the terminal ileum to the ascending colon (ileopexy) or an appendectomy to encourage fixation of the cecum37 (level 5); however, these procedures did not necessarily decrease the recurrence rate37,142–144 (level 3b, 4). These procedures may even be harmful causing local abscess or intestinal adhesion.

CQ50: Do laparoscopic procedures have an advantage?

A: Earlier start of oral intake and shorter hospitalization can be expected following laparoscopic procedures in comparison with open procedures (recommendation C1).

There is no significant difference in operation time or complications between laparoscopic procedures and open surgery. There are reports of shorter hospital stay and earlier oral intake in the laparoscopic group compared with the open surgery group145–147 (level 3b). Disadvantages of laparoscopic procedures include bowel wall injury and difficulty in identification of PLP. Conversion to open surgery is seen in about 12.5–32% of cases144–147 (level 4). Laparoscopic reduction of intussusception is not covered by health insurance in Japan at present.

Ancillary