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Randomised controlled trial of ultrasonography in diagnosis of acute appendicitis, incorporating the Alvarado score

Charles D Douglas, surgical registrar ^a, Neil E Macpherson, medical student ^b, Patricia M Davidson, associate professor of paediatric surgery ^b, Jonathon S Gani, senior lecturer ^b. 

^a Department of Surgery, John Hunter Hospital, NSW 2310, Australia, ^b Faculty of Medicine and Health Sciences, University of Newcastle, Callaghan NSW 2308, Australia

Correspondence to: CD Douglas cdouglas{at}hunterlink.net.au

	Abstract

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Objectives: To determine whether diagnosis by graded compression ultrasonography improves clinical outcomes for patients with suspected appendicitis.
Design: A randomised controlled trial comparing clinical diagnosis (control) with a diagnostic protocol incorporating ultrasonography and the Alvarado score (intervention group).
Setting: Single tertiary referral centre.
Participants: 302 patients (age 5-82 years) referred to the surgical service with suspected appendicitis. 160 patients were randomised to the intervention group, of whom 129 underwent ultrasonography. Ultrasonography was omitted for patients with extreme Alvarado scores (1-3, 9, or 10) unless requested by the admitting surgical team.
Main outcome measures: Time to operation, duration of hospital stay, and adverse outcomes, including non-therapeutic operations and delayed treatment in association with perforation.
Results: Sensitivity and specificity of ultrasonography were measured at 94.7% and 88.9%, respectively. Patients in the intervention group who underwent therapeutic operation had a significantly shorter mean time to operation than patients in the control group (7.0 v 10.2 hours, P=0.016). There were no differences between groups in mean duration of hospital stay (53.4 v 54.5 hours, P=0.84), proportion of patients undergoing a non-therapeutic operation (9% v 11%, P=0.59) or delayed treatment in association with perforation (3% v 1%, P=0.45).
Conclusion: Graded compression ultrasonography is an accurate procedure that leads to the prompt diagnosis and early treatment of many cases of appendicitis, although it does not prevent adverse outcomes or reduce length of hospital stay.

	Introduction

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Acute appendicitis is one of the commonest surgical emergencies. Simple appendicitis can progress to perforation, which is associated with a much higher morbidity and mortality, and surgeons have therefore been inclined to operate when the diagnosis is probable rather than wait until it is certain.¹ A clinical decision to operate leads to the removal of a normal appendix in 15% to 30% of cases (although the figure may be higher or lower in certain demographic groups).¹ This proportion may be reduced by observing equivocal cases for a period of time, a practice that seems to be safe for most patients.² Some cases of appendicitis may resolve spontaneously. ^{3 4} None the less, if a period of observation culminates in the diagnosis of a ruptured appendix, the patient may have suffered a poor outcome that was avoidable. Reductions in the number of "unnecessary" or non-therapeutic operations should not be achieved at the expense of an increase in number of perforations.⁵

It has been claimed that diagnostic aids can dramatically reduce the number of appendicectomies in patients without appendicitis, the number of perforations, and the time spent in hospital.¹ Methods advocated to assist in the diagnosis of appendicitis include laparoscopy, ^{6 7} scoring systems, ^{8 9} computer programs,¹⁰ ultrasonography,¹¹ computed tomography,¹² and magnetic resonance imaging.¹³ Imaging techniques have been shown to be particularly accurate.¹⁴ Graded compression ultrasonography is the least expensive and least invasive of these and has been reported to have an accuracy of 71% to 95%,¹⁴ but doubts have been raised about the influence of ultrasonography on patient outcomes.¹⁵ Furthermore, it has been argued that findings at sonography should not supercede clinical judgment in patients with a high probability of appendicitis.¹⁶ This raises questions about whether sonography should be performed at all in patients at high risk and whether there is some reliable means of selecting those who can benefit from imaging.

The Alvarado score is a 10 point scoring system for the diagnosis of appendicitis based on clinical signs and symptoms and a differential leucocyte count (see table 5). In his original paper Alvarado recommended an operation for all patients with a score of 7 or more and observation for patients with scores of 5 or 6.⁸ Subsequent prospective studies have suggested that the Alvarado score alone is inadequate as a diagnostic test, ^{17 18} but it has been advocated as a means of selecting patients who should undergo imaging.¹⁹

We designed a diagnostic protocol incorporating graded compression ultrasonography and the Alvarado score on the basis of work in our own institution.²⁰ We then undertook a randomised controlled trial to assess whether the information provided by the protocol improved clinical outcomes. We tested the hypotheses that compared with standard treatment patients assigned to the diagnostic protocol would have a shorter mean duration of hospital stay; a lower rate of unnecessary (non-therapeutic) operations; a shorter mean time to surgery for those undergoing therapeutic operations; and an equal or lower rate of delayed treatment in association with perforation.

	Methods

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Ethics committee approval was obtained for this trial. Patients were considered for inclusion in the study if they were referred to the surgical service at John Hunter Hospital and John Hunter Children's Hospital with a provisional diagnosis of acute appendicitis between October 1997 and October 1998. All general surgeons (six), paediatric surgeons (three), and their registrars (seven) at the participating hospital were involved in the study.

Patients were excluded from randomisation if they fulfilled any of the following criteria: age less than 5 years; evidence of generalised peritonitis; palpable mass in the right iliac fossa; evidence of acute confusional state or dementia; graded compression ultrasonography already performed. All other patients were met by the project officer, a third year medical student, who explained the study and obtained consent. The project officer randomly allocated patients by coin toss to control (standard treatment) or diagnostic protocol (intervention) groups. He organised a leucocyte count and performed a structured clinical assessment from which he calculated the Alvarado score (modified only by using percussion tenderness in the place of rebound tenderness).

For patients in the control group, members of the admitting surgical team were not informed of the Alvarado score. They proceeded with appropriate clinical assessment and management. They were requested not to organise graded compression ultrasonography for 36 hours.

For patients in the intervention group, the project officer advised the admitting team of the Alvarado score. Ultrasonography was then organised if the Alvarado score was between 4 and 8, inclusive. An Alvarado score of 9 or 10 was taken to be a relative indication for surgery, but the admitting team was given the option of organising graded compression ultrasonography; patients with an Alvarado of 3 or less were not eligible for ultrasonography. The admitting team was advised of the result of ultrasonography when this was done.

Ultrasonography
Graded compression ultrasonography results were designated positive, negative, or equivocal by the attending sonographer by using the following criteria: positiveappendix identified, tender and non-compressible or appendiceal phlegmon or abscess seen; negativeappendix not identified, no other relevant abnormality seen; equivocalappendix not identified but abnormal amount of free fluid seen with thickened, dilated, or non-peristaltic bowel in the region of the caecum. In our experience these latter findings are often associated with perforation, and we suggested to participating surgeons and registrars that it was safest to consider such a report as a positive result.

Surgery
All patients who underwent laparotomy or laparoscopy for suspected appendicitis had an appendicectomy. The diagnosis of appendicitis was made on histological grounds on the basis of infiltration of the muscularis propria by neutrophil granulocytes.

Perforations
The appendix (or bowel) was considered to be perforated if the surgeon clearly identified a perforation or a peritoneal swab grew at least one definite bowel organism or the histopathologist identified a perforation in association with gangrene or full-thickness necrosis.

Delayed treatment in association with perforation
For patients with perforation, treatment was considered to be delayed if surgery had not started within 10 hours of randomisation.

Follow up
Patients were reviewed at one week and three months with a pro-forma assessment. When direct review was not possible, details were obtained from the patient's general practitioner or surgeon.

Outcomes
We identified four outcome measures.

Power
This sample had a power of 80% to detect a difference between groups of 3.3 hours for mean time to theatre, 15.2 hours for mean duration of stay, and a reduction in the non-therapeutic operation rate from 11% to 2%.

Data analysis
Data were analysed on an intention to treat basis. For calculation of sensitivity and specificity of graded compression ultrasonography we included cases only if a histological diagnosis was available. Diagnoses other than appendicitis were ignored. Equivocal ultrasonography reports were counted as positive. Thus if the results of graded compression ultrasonography were reported as positive or equivocal for appendicitis but a perforated diverticulum and normal appendix were found at operation, the test was counted as a false positive, even though the operation was considered therapeutic.

	Results

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Figure 1 shows the trial profile. In total 306 patients were referred for inclusion; two patients failed to meet inclusion criteria and two patients refused consent, thus 302 patients were enrolled in the study, with 160 in the intervention group and 142 in the control group. The mean age was slightly lower in the intervention group (20.2 v 23.5 years); 202 patients were aged 14 years and over and 100 were aged under 14 years. There was little difference between groups with respect to sex, mean Alvarado score, or proportion with Alvarado score greater than 6. Figure 2 shows the distribution of Alvarado scores. Table 1 summarises the results. Subgroup analysis by age is shown in table 2.

View larger version (30K): [in this window] [in a new window]   Fig 1.   Profile of trial of graded compression ultrasonography and Alvarado score compared with clinical methods in diagnosis of appendicitis

Sixteen patients were in breach of the trial protocol because the admitting surgeon in each case thought that this was in the patient's interests. All were included in the reported analysis on an intention to treat basis. The results of a secondary analysis with these patients excluded were not substantially different with respect to adverse outcomes (intervention 17/154 (11%; 95% confidence interval 7% to 17%) v control 16/132 (12.1%; 8% to 19%); P=0.8) or duration of stay (intervention 53.1 (46 to 60) hours v control 53.0 (44 to 62) hours; P=0.99).

View larger version (24K): [in this window] [in a new window]   Fig 2.   Distribution of Alvarado scores in patients with suspected appendicitis allocated to diagnosis with graded compression ultrasonography and Alvarado score (intervention group) or clinical diagnosis only (control)

Ultrasonography
Graded compression ultrasonography was performed in 139 patients (see table 3). The sensitivity and specificity of ultrasonography for diagnosing appendicitis was 94.7% and 88.9%, respectively. There were three false negative results. Six patients with a positive or equivocal result on ultrasonography recovered without surgery.

Surgery
There were 170 operations performed: 95 of the 160 patients in the intervention group underwent surgery compared with 75 of the 142 patients in the control group (59.4% v 52.8%, P=0.25). Appendicitis was confirmed histologically in 128 patients: 73 (45.6%; 38% to 53%) in the intervention group and 55 (38.7%; 31% to 47%) in the control group (P=0.23). There were 13 patients with other conditions that met the criteria for a therapeutic operation (see table 4). Twenty nine operations were non-therapeutic: 14 (8.8%; 5.3% to 14.2%) in the intervention group and 15 (10.6%; 6.5% to 16.7%) in the control group (P=0.59).

Perforations
Twenty four patients had perforations, 19 had a perforated appendicitis (14.8% (10% to 22%) of all cases of appendicitis) and five had other bowel perforations. Of all perforations, 14 were in the intervention group and 10 in the control group (perforations/number in group of 8.8% (5.3% to 14%) and 7.0% (3.9% to 12%), respectively, P=0.58).

Delayed treatment in association with perforation
There were seven cases of delayed treatment in association with perforation (six cases of appendicitis and one of perforation of a caecal carcinoma). Five of these were in the intervention group and two were in the control group (3.1% v 1.4%, P=0.45, Fisher's exact test).

Follow up
There were no readmissions with appendicitis during the follow up period. Two patients required readmission for complications: one in the intervention group for drainage of an abscess and one in the control group for an early small bowel obstruction. Nine patients had minor wound infections diagnosed one week after discharge (4 v 5, P=0.51, Fisher's exact test). Four patients were lost to follow up at three months, three of whom had had their appendix removed during their admission (and were therefore able to be analysed for all end points); the fourth, in the control group, had had a negative result on ultrasonography before discharge.

	Discussion

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We have confirmed the high sensitivity and specificity of graded compression ultrasonography in the diagnosis of appendicitis. All our patients who underwent surgery after a positive result on ultrasonography proved to have appendicitis. Patients with equivocal signs of appendicitis are usually admitted to hospital for a day or night of observation. If the result on graded compression ultrasonography is positive, however, the surgeon can operate immediately. In our study, this lead to a significant reduction in mean time to therapeutic operation.

As some cases of appendicitis seem to resolve without surgery, ^{3 4} however, graded compression ultrasonography could lead to an increase in therapeutic operations (by correctly diagnosing appendicitis in patients who may have recovered during a period of observation). Our results are consistent with this, with a higher proportion of therapeutic operations occurring in the intervention group, although the difference was not significant. This is despite the fact that Alvarado scores were similarly distributed between groups.

The reduced time to operation in the intervention group did not result in a reduced duration of hospital stay. There was a trend towards shorter stays in the intervention group for patients undergoing therapeutic operations but because a larger proportion of the control group was managed non-operatively (and therefore discharged early) there was no difference overall.

Adverse outcomes
There are two outcomes that surgeons seek to avoid in cases of suspected appendicitis. The first is a non-therapeutic operation. The second is delayed treatment in a patient who is subsequently found to have perforation (delayed treatment in association with perforation). In this study, the proportion of patients in each group who had an adverse outcome (either a non-therapeutic operation or delayed treatment) was similar. The occurrence of a number of cases of delay with perforation, despite a low rate of perforated appendicitis (14.8%), suggests that rate of delayed treatment in association with perforation is a more appropriate measure of the consequences of delayed diagnosis than overall perforation rate.

Use of the Alvarado score to select patients for imaging
We used the Alvarado score as an objective means of stratifying patients according to risk so that those with a high or low probability of appendicitis need not have unnecessary imaging. The Alvarado score (table 5) is based on a simple and largely objective assessment that requires minimal clinical experience, nevertheless NEM had an intensive period of training before the study began, and we ensured that he was eliciting symptoms and signs in a consistent and objective way. We believe that having one person perform the same objective assessment on all occasions was a reliable and reproducible method of risk stratification.

Possible biases
Distributions of Alvarado scores in each group were similar, and the proportions of each group with an Alvarado score of greater than 6 (that is, patients who would be predicted to have appendicitis on the basis of Alvarado's original paper) were almost identical. Therefore the disparity between groups in number of therapeutic operations performed is unlikely to reflect a difference in disease prevalence.

General comments
When performed by experienced sonographers, graded compression ultrasonography is an accurate test. In this trial the accuracy was over 93%, equal to that of computed tomography without colonic contrast.¹⁴ False negative reports, however, do occur: in our study 5% of negative results were incorrect. There is no certain way of determining which negative result is a false negative, and the consequences of not operating may be serious. Patients cannot be safely sent home after a negative result unless there are also clinical grounds for their discharge. It is therefore inappropriate for graded compression ultrasonography to be used by those who lack experience in the clinical diagnosis of appendicitis.

Conclusion
The diagnosis of acute appendicitis aided by graded compression ultrasonography has not been shown to produce better outcomes than clinical diagnosis alone. Further studies of graded compression ultrasonography and other diagnostic methods in suspected appendicitis should be randomised trials.

	Acknowledgments

We thank Dr John Bear and Dr Jan Bishop for assistance with sonographic and histopathological diagnosis. We also thank sonographers Sue Mullen, Jenny Gosling, Warren Jones, Brett Roworth, and Darrin Gray for their excellent technical assistance. In addition we thank Professor Michael Hensley, who reviewed the proposal for study design and gave advice about data interpretation and analysis, and Dr Brian Draganic, who gave statistical advice and reviewed and edited the drafted paper.

Contributors: CDD initiated the study, formulated the study hypotheses, proposed the study design, analysed the data, was the principal author of the paper, and is the guarantor. NEM managed the running of the trial, contributed to study design, collected the data, initiated and participated in data analysis, and helped to write the paper. PMD initiated the research in ultrasonography, supervised the running of the trial, facilitated and coordinated involvement of different departments, contributed to data interpretation, and helped to edit the paper. JSG contributed to study design, supervised the running of the trial, contributed to data interpretation and analysis, and helped to write and edit the paper.

	Footnotes

Funding: None.

Competing interests: None declared.

	References

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(Accepted 18 May 2000)