Gastro-oesophageal reflux disease in institutionalised intellectually disabled individuals

‘fhe Setherland5

JOURNAL OF MEDICINE

ELSEVIER

Netherlands

Journal

of Medicine

5 1 (1997)

134- I39

Original article

Castro-oesophageal reflux disease in institutionalised intellectually disabled individuals C.J.M. Biihmer a,13b, M.C. Niezen-de Boer a, E.C. Klinkenberg-Knol b, J.H.S.M. Nadorp ‘, S.G.M. Meuwissen b,* b Free

University

a Bartime’us, Institute for Intellectually Disabled, &is& Netherlands Hospital, Department of Gastroenterology, de Boelelaan 1117, 1081 HVAmsterdam, ’ Antonius Hospital, Department of Gasfroenterology, Nieuwegein, Netherlands Received

13 January

1997: revised

27 May

1997; accepted

28 May

Netherlands

1997

Abstract Background. The prevalence of reflux oesophagitis (RO) in the normally intellectual population is about 2%, while this condition in the intellectually disabled has an estimated prevalence of 10%. Methods. We investigated the presence of RO among 1687 intellectually disabled, with an IQ < 50, from 5 different institutes in the Netherlands. All were scored for possible associatedfactors and reflux symptoms, and compared with the overall population (n = 1580) from the same institutes (controls). Also, the effect of treatment on symptoms was evaluated after at least one year of therapy. Results. Gastro-oesophagealreflux disease (GORD) was suspected clinically in 169 patients based on the following symptoms: vomiting, haematemesis,anaemia, rumination or behaviour problems. At endoscopy RO was diagnosed in 107 of 1687 patients (6.4%): 17 (15.9%) grade I, 34 (31.8%) gr. II, 42 (39.3%) gr. III and 14 (13.1%) gr. IV RO (Savary-Miller classification). Cerebral palsy, constipation, anticonvulsant drugs, an IQ < 35, underweight and gastrostomy feeding appeared to be possible associatedfactors, while as reflux symptoms persistent vomiting, haematemesis, iron deficiency anaemia, rumination, and behaviour problems were found. Concerning therapy, surgery was found to be effective in 38%, H, receptor antagonistsin 60% and the proton-pump inhibitor omeprazole in 96%. Conclusions. In this group of Dutch intellectually disabled patients with IQ < 50 RO was diagnosed in about 6% (107 of 1687), mostly severegrades of oesophagitis.Severalpossibleassociatedfactors were significantly present. From non-specific reflux symptoms persistent vomiting was the most indicative factor. In this population the most effective treatment of RO was long-term omeprazole therapy. 0 1997 Elsevier ScienceB.V. Keywords:

Intellectual

disability;

Gastro-oesophageal

reflux

disease:

Omeprazole

effective

1. Introduction

* Corresponding author. Tel.: +31 20 4440613; 4440554. ’ Present address: Medisch Centrum Alkmaar, Geneeskunde, Wilhelminalaan 12, 1815 JD Alkmaar, 0300-2977/97/$17.00 0 1997 Elsevier PII SO300-2977(97)00055-7

Science

fax:

B.V.

Gastro-oesophageal reflux disease (GORD) describes the condition in patients who have symptoms or other problems arising from pathological reflux of acid gastric contents into the oesophagus. This ab-

+ 31 20

Afd. Inteme Netherlands. All rights

reserved.

C.J.M.

Bijhmer

et al/Netherlands

normal acid exposure often leads to reflux oesophagitis (RO). In 4-10% of the normally intellectual adult Westem population GORD is suspected, based on classical symptoms, particularly heartburn [ 1,2], while 2% of the Western population showed RO [3,4]. In the intellectually disabled GORD is more often found than in the normally intellectual population [5-71. Previous studies mentioned that lo-25% of institutionalised disabled subjects have symptoms of vomiting [8], regurgitation [8,91 or rumination [.5,6,10,11], while GORD was diagnosed in up to 75% in this symptomatic population [ 111. In the intellectually disabled the diagnosis of GORD will often be delayed. This is due to the fact that in this population other symptoms than in the normally intellectual population indicate GORD, such as pulmonary problems (i.e., recurrent aspiration or chronic obstructive pulmonary disease (COPD) [12141, failure to thrive with poor growth and inadequate nutritional condition. Secondly, invasive procedures, like endoscopy, are generally believed to be too stressful for the intellectually disabled. As a consequence of this diagnostic delay, complications are frequently seen, like iron deficiency anaemia due to microscopic faecal blood loss or overt gastrointestinal bleeding [ 10,151, complicated RO like ulceration, strictures [ 16,171, and Barrett’s oesophagus [ 101. Therefore, in this study we wanted to evaluate retrospectively the presence of endoscopically diagnosed RO and the symptoms on which the diagnosis was based. Further, we analyzed possible associated factors to develop RO. Also, we evaluated the effect of different therapeutic regimens on symptom relief.

2. Materials and methods 2.1. Patients and controls

We investigated the presence of RO among the total population, including 2162 intellectually disabled, from five different institutes in the Netherlands by retrospective dossier research. All individuals were tested with an IQ score following the International Classification of Diseases (ICD-10) by clinical psychologists of the different institutes. With this IQ score the level of intellectual

Journal

of Medicine

51 (1997)

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135

disability was classified in three groups: an IQ between 50 and 70 was defined as mild intellectual disability, an IQ between 35 and 50 as moderate intellectual disability, and an IQ < 35 as severe or profound intellectual disability (World Health Organisation). 475 individuals with an IQ > 50 were excluded because they were suggested to be able to express their discomfort comparable to the normally intellectual population. Patients were defined as intellectually disabled subjects with an IQ < 50 and endoscopically proven RO (n = 107). Controls were intellectually disabled from the same institutes in whom RO was not suspected, and endoscopy not performed (n = 1580). 2.2. Methods

The incidence of RO, diagnosed by endoscopy, was evaluated. The severity of RO, following the Savary-Miller classification, and the rate of complications, such as ulceration, Barrett’s oesophagus and strictures were scored. All 1687 intellectually disabled with an IQ < 50, were scored for ‘possible associated factors’ and ‘possible reflux symptoms’ retrospectively from the case records by the research physician with the assistance of the physician of the institute, who examined the patient at the time of the investigation. Afterwards patients and controls were compared. Possible associated factors indicated from literature research included: non-ambulancy, scoliosis, cerebral palsy, constipation, use of anticonvulsant drugs including all benzodiazepin medication, an IQ < 35, length, weight, nasogastric tube feeding and gastrostomy feeding. Non-ambulancy was defined as at most being semi-ambulant and able to move only with help of others. Scoliosis was concluded to be present as severe kyphosis or moderate and severe kyphoscoliosis. Cerebral palsy was defined to be present as hemiplegia, tetraplegia, quadriplegia and overall hypotonia. Constipation was defined as a bowel movement less than 3 times a week without laxatives. Possible reflux symptoms in intellectually disabled are mentioned: persistent vomiting, haematemesis, iron deficiency anaemia, rumination, regurgitation, behaviour problems as episodes of screaming, aggression, fear or restlessness. The

symptoms were defined to be present when they appeared at least 4 times a month. A haemoglobin decrease of more than 2 mmol/l and hypochromia was defined as iron deficiency anaemia. Also scored as other possible associated factors were age and gender. Retrospectively, the effect of treatment, surgical or medical, was evaluated from the case records by the research physician with the assistance of nursing and clinical staff of the institute, by scoring the symptoms, such as persistent vomiting, haematemesis, iron deficiency anaemia, rumination, and behaviour problems, present at the time of the endoscopy and after at least one year of treatment. Symptom free was defined as the appearance of possible reflux symptoms less than 4 times a month. Treatment effect was analyzed retrospectively from treatment protocols defined by the physician of the institute. Forty patients used cimetidin (800 mg b.d.) or ranitidin (300 mg b.d.1 during at least 6 weeks to maximal 3 months, followed in 18 patients by longterm therapy, cimetidin (400 mg o.d.1 or ranitidin (150 mg 0.d.). In 46 patients omeprazole 40 mg once daily (0.d.) was used during 6 weeks followed by 20 mg (0.d.) for 6 weeks and continued as maintenance therapy.

3. Statistical analyses Chi-square test and Fisher’s exact probability test were used for statistical evaluation, and P < 0.05 was considered as significant.

241 women; mean age: 36.2 years, range 6-92 years) the IQ was scored between 35-50. Based on clinical symptoms, as defined in Section 2.2, GORD was suspected in 169 out of 1687 (10.0%) intellectually disabled. They underwent endoscopy (87 with local anaesthetics and 82 under general anaesthesia). RO was found in 107 of 169 (63.3%) intellectually disabled. Following the Savary-Miller classification grade I was detected in 17 (15.9%) of the patients, in 34 (31.8%) gr. II, in 42 (39.3%) gr. III and in 14 (13.1%) gr. IV was diagnosed (Fig. 1). Complications of long-standing GORD were found in 21 (19.6%) of the cases, of whom 16 (15.0%) showed a Barrett’s oesophagus and 5 (4.7%) peptic strictures. 4.2. Symptoms and associated factors scores 4.2.1. Associated factors CTable I! Cerebral palsy, constipation, use of anticonvulsant medication, an IQ < 35, gastrostomy feeding and underweight were significantly more found in patients compared to controls. 4.2.2. Rejlux symptoms (Table 1) Persistent vomiting, haematemesis, iron deficiency anaemia, rumination, regurgitation and behaviour problems were the most frequent indications for endoscopy. All of these symptoms, except regurgitation, were significantly more often found in patients compared to controls.

4. Results 4.1. Prevalence of RO The total population of five institutes included 2 162 intellectually disabled individuals. All subjects were divided into three groups by IQ scoring. 475 persons (302 men, 173 women; mean age: 37.6 years, range: 12-82) had an IQ > 50 and were excluded from further evaluation. 1078 inhabitants (668 men, 410 women; mean age 34.8 years, range 2-78) had an IQ < 35, while in 609 individuals (368 men,

I

II

III

IV

GRADE Fig. 1. Endoscopic findings following the Savary-Miller cation in intellectually disabled patients.

classifi-

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et al/Netherlands

Journal

Table 1 Associated factors and reflux symptoms for developing RO in intellectually disabled individuals Patients Controls P (No. and %) (No. and %) Associated

factors

Non-ambulant Scoliosis Cerebral palsy Constipation Anticonvulsant drugs IQ < 35 Nasogastric tube Gastrostomy feeding Underweight Adiposities Age (mean, years) Gender Men Women Reflux symptoms Vomiting Haematemesis Anaemia Rumination Regurgitation Changed behaviour

47 (43.9) 51 (47.7) 52 (48.6) 68 (63.6) 63 (58.9) 86 (80.4) 4 (3.7) 17 (15.9) 38 (35.5) 19 (17.8) 38.4

600 (38.0) 632 (40.0) 600 (38.0) 521 (33.0) 452 (28.6) 1033 (65.4) 101 (6.4) 62 (3.9) 325 (20.6) 393 (24.9) 35.3

ns ns = 0.03 < 0.0001 < O.c@Ol = 0.01 ns < 0.0001 = 0.001 ns ns

64 (59.8) 43 (40.2)

899 (56.9) 681 (43.1)

ns ns

90 34 37 43 39 43

221 (14.0) 142 (9.0) 237 (15.0) 158 (10.0) 458 (29.0) 859 (54.4)

< 0.0001 < 0.0001 < 0.0001 < 0.0001 ns = 0.01

(84.1) (31.8) (34.6) (40.2) (36.4) (40.2)

of Medicine

51 (1997)

Eighty-six out of 107 patients (80.4%) were treated medically. In 40 out of 107 patients (37.4%) H, receptor antagonists were used during at least 6 weeks to maximal 3 months. After this period, 18 cases (45.0%) out of 40 received long-term therapy. With this regimen 24 (60.0%) out of 40 became symptom-free, of whom 11 (45.8%) used long-term medication. Forty-six (43.0%) received omeprazole 40 mg (o.d.1 during 6 weeks followed by 20 mg (0.d.) as maintenance therapy. With this regimen 44 (95.7%; 49.2% gr. III or IV) out of 46 became symptom free. In none of them was endoscopic evaluation performed.

5. Discussion

Patients, n = 107; controls n = 1580.

4.3. Response to different treatment regimens (Table 2) Twenty-one of 107 patients (19.6%), all grade III or IV RO, underwent antireflux surgery: i.e., a laparatomic Nissen procedure. After a median of 38.6 (range 14-96) months of follow-up, 8 (38.1%) patients were symptom free. Thirteen (61.9%) showed no clear improvement of their symptoms.

This study shows that, in this large group of intellectually disabled individuals in the Netherlands, GORD was suspected in lo%, while RO was demonstrated in 63% of these suspected cases. However, we must state that in the group without evident symptoms no endoscopies were performed; therefore, it is possible that the problem of GORD is underestimated. One, smaller study in the Netherlands showed that GORD was suspected in 42 of 573 (7.3%) intellectually disabled subjects, while at endoscopy only 16 (38.1%), were shown to have RO (van de Wiel, 1994, unpublished data). Our results are more in concordance with extensive data from the literature, where GORD has been suggested to be present in 75% [6] of all intellectually disabled who have regular symptoms of vomiting [5,8,13,17], rumination [5-7,101, or regurgitation [8,9,11].

Table 2 Treatment of reflux oesophagitis in intellectually disabled patients, based on (subjective) symptom scoring Treatment Number of patients Clear improvement No clear improvement (No. and %) (No. and %) (No. and %) Surgical Medical H, blockers Proton-pump inhibitors

131

134-139

P

21(20)

8 (38)

13 (62)

0.01 a

40 (37) 46 (43)

24 (60) 44 (96)

16 (40) 8 (4)

< 0.001 b

Patients n = 107. L Surgical therapy compared to medical therapy. H, blockers compared to proton-pump inhibitors,

In the group of intellectually disabled persons with RO, 39% and 13% showed grade III and grade IV oesophagitis, respectively, complicated in nearly 20% as a Barrett’s oesophagus or peptic stricture. In the normally intellectual population, Barret’s oesophagus is demonstrated in lo- 15% of patients with oesophagitis [ 19-221 and peptic stricture in 9-15% [3,22]. In contrast, complications in intellectually disabled persons are more frequently described: the presence of a Barrett’s oesophagus in 1 l-44% of GORD patients [lo] and peptic stricture in 7-25% [ 16,181 of patients. In this study, however, we did not find significant differences for these complications, comparing our population with the normally intellectual population. Associated factors for RO in this study appeared to be cerebral palsy, scoliosis, constipation, use of anticonvulsant drugs, an IQ < 35, underweight and gastrostomy feeding. Our results are partly in agreement with those obtained by van Winckel, who also demonstrated a relation between cerebral palsy and RO, but not between level of intellectual disability and RO 1141. The mechanism by which these associated factors work can be explained by their influence on the lower oesophageal sphincter (LOS), the most important part in the prevention of gastro-oesophageal reflux. The sphincter tone differs considerably during the day, and particularly decreases in relation to ingestion of food, and after anticholinergics or sedative therapy. An incompetent LOS pressure is observed in cases of increased intra-abdominal pressure as adiposities, constipation and coughing, but also in non-ambulatory individuals [ 151, subjects with scoliosis with or without plaster corsets [23] or spastic quadriplegia (cerebral palsy). Probably, the abdominal compression is an important contributing factor for RO [8,1 I]. However, we could only demonstrate a relationship between GORD and constipation and cerebral palsy. GORD in both intellectually and physically disabled is often overlooked, because symptoms are often unclear and aspecific [14,24,25]. Symptoms of vomiting, regurgitation or rumination are associated with GORD in lo-25% [5,6,11]. In agreement with these results, Van Winckel found that persistent vomiting and behaviour problems are potential associated factors for RO [14]. Our study demonstrates that persistent vomiting, rumination and behaviour

problems are symptoms indicating RO, but a relation between regurgitation and RO was not established. Failure of medical therapy in intellectually disabled individuals appears to occur frequently, particularly with antacids and Hz receptor antagonists [7,10]. In these publications nearly half of the patients showed no improvement of their symptoms. Over the past 20 years. antireflux surgery has been applied as treatment of choice in the intellectually disabled, despite a higher mortality rate (> lo%), a higher frequency of postoperative complications ( > 50%) and a need for reoperation in over 20% compared to the intellectually normal population [26,27]. Failure of medical treatment has always been an indication for surgery, although medical treatment has never been optimised. In contrast, omeprazole is in the normal adult population the therapy of choice with high healing rates [28,29]. Also, it has recently been shown to be effective and safe for the treatment of severe RO in children resistant to other medical treatment or where surgery has failed [30]. In our population we compared the different treatment regimens used for the healing of RO, based on subjective reflux symptom scores. Surgery, antacids, and Hz receptor antagonists showed low healing rates. Only the proton-pump inhibitor omeprazole was effective in most cases, even in complicated oesophagitis. however we must state that in all cases no control endoscopy was performed. In conclusion, this study shows that RO is a major clinical problem in the intellectually disabled population. Prospective studies for adequate diagnostic regimens are certainly needed and are at present in progress to obtain more accurate data about prevalence, associated factors, reflux symptoms and evaluation of the effect of omeprazole therapy.

Acknowledgements This study was made possible through the help and cooperation of the medical staff of the five following institutes: Bartimeushage, Doorn; Binckhof, Grave; Hartekamp, Heemstede; Reigersdaal, Heerhugowaard; and Westerhonk, Monster, in particular M. Gruyters, A. Idzinga and A.A. Trappenburg.

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et al. /Netherlands

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