A clinical pathway is defined as structured care plan that details essential steps in patient care with specific clinical problems, which supports translation of clinical guidelines into local protocols and clinical practice . Clinical pathways aim to standardize the diagnosis process, treatment approach, decrease the length of hospital stay and reduce the healthcare costs  .
Acute appendicitis (AA) is one of the most common surgical diseases. The estimated lifetime incidence of AA is 7%. Despite its high prevalence rate, the diagnosis of AA is challenging due to the disease progression leading to the absent of the classical symptoms and sign of the disease which might lead eventually in delaying of the diagnosis and results in complications  . Several studies have demonstrated the benefits of standardized protocol for appendicitis management to reduce the rate of morbidity and mortality   . Due to an absence of standardized protocol, management of AA relies on surgeon preference. Variability in surgeons’ preference is related to the variation of the disease’s clinical pattern     .
Given the high incidence rate, there is a need for a simple, precise, and clear clinical procedure to standardize the management approach and improve the clinical outcome. This review aims to assess the available literature on the impact of the implementation of standard AA management clinical pathways on clinical outcomes and patient experience.
2. Materials and Methods
A systematic review protocol was created in accordance with the Preferred Reporting Items for Systematic Reviews and Meta-Analysis (PRISMA) statement . With this review’s aim in mind, we attempted to extract the following parameters from eligible literature: clinical pathway components used in each study and outcomes used to assess the pathway.
We first extracted information from a clinical engine search (PubMed, Medline, and Cochrane Library) to find available literature meeting the initial entry criteria published between 1974 and December 2012. Then, the bibliography of each study was reviewed for additional sources. The search terms used were “appendicitis,” “appendectomy,” “appendix,” or “append” and “managed care program,” “standards,” “clinical pathways,” or “clinical protocols.” The eligibility criteria for inclusion were studies that investigated clinical pathways for appendicitis in human subjects. Only original articles that were published in English were included and assessed.
Validation of eligibility was achieved through two stages by two reviewers. At the first stage, the first reviewer screened abstracts of extracted studies for at least one of the following keywords; appendicitis, appendectomy, appendix, append*, managed care programs, standards, clinical pathways, or clinical protocols. The second reviewer screened abstracts to ensure that the screening process was robust. Full articles of abstracts that had passed the initial screening process and abstracts that were reserved for full article review were reviewed to determine eligibility. In the second stage, full articles were examined and validated. Publications were excluded if they were animal or in-vitro studies, not published in the English language and for which a translated version was not available, did not involve a clinical pathway for appendicitis management, or was published as a case report, letter, comment, or reviews.
Eligible studies were reviewed, and information was extracted about participants’ characteristics (age, gender, body mass index, etc.), components of clinical pathways (preoperative, intraoperative, and postoperative), and clinical pathway outcomes (length of stay, complications, cost, etc.). Data extraction was performed by two reviewers independently and entered into a spreadsheet. Both data sheets were then merged for validation. The discrepancy was then resolved by consensus with reference to the original article or expert consultation.
3.1. Study Selection
A total of 1079 articles were extracted; 1070 articles were identified from search engines, and 9 articles were identified by manual search. After the exclusion of duplicated papers, a total of 861 abstracts were screened and 100 articles were identified to be eligible. Full article assessment indicated that 51 articles were eligible for the final validation process. A total of 37 studies were included in the systematic review. Figure 1 presents the PRISMA diagram.
3.2. Study Characteristics
A total of 37 articles were reviewed. Articles were classified based on design into prospective studies (22/37), retrospective studies (14/37) and case control studies (1/37). Most of the studies were conducted in North America, 3 studies took place in Europe, and 7 studies took place in other countries (Australia, India, Israel, Japan, and Turkey). The sample size varied between 30 and 2218 subjects. An assessment of extracted literature based on the age classification of the study population indicated that 24 studies were carried out with a pediatric population, 10 studies were carried out with an adult population, and 3 studies were with both categories. The mean age for non-complicated appendicitis was nearly comparable in the intervention and control groups (18.19 years and 19.70 years, respectively). For all reviewed studies, most of the study population was male, with the exception of one study that had enrolled only females (the author reported intraoperative for incidental laparoscopic appendectomy during gynecological procedure). Table 1 summarizes studies included in this review.
3.3. Pathway Elements
3.3.1. Pre-Operative Pathway
A clinical pathway is classified based on the onset into preoperative, intraoperative, and postoperative pathways. Regarding preoperative pathways, a clear definition for appendicitis pathway was observed in 30 articles. Initial diagnosis of
Figure 1. PRISMA figure.
Table 1. Summary of studies assessed.
appendicitis was based on clinical evaluation and laboratory findings. Some studies involved radiological assessments to support diagnosis. Ultrasound was used in 8 studies, and 12 studies used a computed tomography (CT) scan. Preoperative antibiotic was documented in 13 studies; however, the antibiotic regimen varied. An age-appropriate pain scoring system in the preoperative protocol was documented in one study . In this study, 72.7% of the protocol had a formal pain assessment compared to 31.30% of the pre-protocol group. Preoperative family education and counseling involved plans for early discharge from post-anesthesia care unit and postoperative instructions were given to families . Nevertheless, some studies carried family education out postoperatively . Only 4 studies administered pregnancy tests and only one study documented performing blood culture preoperatively in patients with complicated appendicitis . Table 2 summarizes findings for preoperative pathways.
3.3.2. Intra-Operative Pathway
Despite the popularity of laparoscopic techniques among surgeons and patients, laparoscopic appendectomy was performed in about 64.4% patients. In this review,
Table 2. Components of preoperative pathways.
*Mentioned patients diagnosed with appendicitis but not clear how? Or not mention the word clinically. #A retrospective perforated appendicitis which diagnosed intraoperative.
two studies reported anesthesia protocol as part of the clinical pathway  . Another two studies on complicated appendicitis documented the use of intra-abdominal drains  . Emil et al. reported the insertion of intra-abdominal drain for non-complicated appendicitis as 0%. Only one study focused on the impact of clinical pathway in minimizing the utilization of intraoperative resources such as a nasogastric tube. The use of nasogastric tubes in patients with perforated appendicitis under the pathway was significantly reduced, while less than 3% of the study population required one during hospitalization . Another study reported a protocol in a case of perforated appendicitis; they irrigated the entire wound with saline and closed the incision with subcuticular suture without drains . Table 3 summarizes components of intraoperative pathways.
3.3.3. Post-Operative Pathway
There was a clear description of discharge criteria in 15 studies (Table 5). The majority of these studies indicated that afebrile status was the main criteria for discharge, other studies suggested pain control with oral analgesia, having normal blood cell count and tolerating an oral diet. Few studies suggested discharge once the patient could tolerate a liquid diet    . Resuming normal bowel function and passing urine were considered essential for discharge. Few studies considered social factors to be key elements in discharge criteria    . Table 4 summarizes components of postoperative pathway.
Table 3. Components of intraoperative pathways.
$: Laparoscopic appendectomy; &: Open appendectomy.
Table 4. Components of postoperative pathways.
The efficacy of the clinical pathway was assessed by determining the length of stay at the hospital. The mean hospital length of stay (LOS) for non-complicated appendicitis varied between studies and ranged between 3.1 and 96 hours. The mean hospital LOS for complicated appendicitis also varied between studies and was in the range of 94.5 and 316.8 hours. All studies concluded that the LOS was shortened among patients who had a clinical pathway implemented in their case. The response time for surgical consultation was between 1.6 and 2.12 hours  . Two studies examined time spent in the ER  .
Recent studies examined the efficacy of pathways by measuring the percentage of patients with same day discharge, ranging between 58% and 92.4%    .
Seven studies showed that the use of clinical pathways is cost-effective in managing patients with non-complicated appendicitis       . Four studies concluded that using a clinical pathway is efficacious in reducing hospitalization costs in cases of complicated appendicitis    . Only 3 studies concluded no impact from the use of a clinical pathway in reducing hospitalization cost of complicated appendicitis   .
Complication rates varied between 0% and 28%. The wound infection rate for noncomplicated appendicitis ranged between 0% and 7.5%, and 0.7% and 13% for complicated appendicitis. The percentage of intra-abdominal abscess for non-complicated appendicitis ranged between 0% and 1.9% and 1.3% and 12.79% for complicated appendicitis.
The rate for post appendectomy emergency department visits ranged from 0% and 13.7%     . Readmission rate in non-complicated appendicitis ranged between 0% and 4.2%.
Although the concept of clinical pathways was first introduced in 1980s, there is yet to be a standardized definition. Lawal et al. established 4 criteria for clinical pathways: fitting into multidisciplinary plan for care, guiding evidence into a structure, detailing the steps throughout the course of the treatment, and standardizing care for a particular population . In this systematic review, reviewers identified 37 articles that defined a treatment algorithm of appendicitis based on this criterion.
4.1. Preoperative Pathway Elements
4.1.1. Preoperative Evaluation
The classic approach for appendicitis diagnosis is based on clinical evaluation supported by laboratory testing with or without imaging; however, the diagnosis of appendicitis remains challenging. In 2016, a randomized multicenter clinical trial recruited 1321 patients and revealed that clinical and laboratory tests were unreliable in diagnosis of acute appendicitis . A CT scan and ultrasound were used in preoperative evaluation of patients presented with suspected appendicitis to assess in diagnosis. In a 2016 retrospective review where 354 adult subjects were recruited, the majority of study sample was female, showing that the ultrasound of surgery-confirmed appendicitis had a sensitivity and specificity of 48.4% and 97.9% respectively . In 2015, a retrospective database analysis of 54,153 children from 35 pediatric institutions in the US found that ultrasound is the first imaging choice for suspected appendicitis at most centers. Moreover, within 2 years, ultrasound use increased by 11.3% and CT scans were used 9.8% less often . A retrospective study with a sample size of 2763 subjects evaluated the efficacy of ultrasound, CT scan and physical examination in acute appendicitis diagnosis. The study found that for ultrasound the sensitivity level was 99.1%, specificity level was 91.7%, the positive predictive value was 96.5% and the negative predictive value was 97.7%. On the other hand, for CT scan the sensitivity level was 96.4%, the specificity level was 95.4%, the positive predictive value was 95.6%, and the negative predictive value 96.3%. The sensitivity of physical examination was 99.0% whereas the specificity was 76.1%, the positive predictive value was 88.1%, and the negative predictive value was 97.6%. Study concluded that imaging studies after negative physical examination could be unnecessary . Another 10-year retrospective analysis with a sample size of 1 366 subjects revealed that performing a preoperative CT scan decreased the rate of negative appendectomy in women younger than 46 years but not in older women or men .
In this review, 64.86% of the studies documented using clinical evaluation and 27% laboratory investigation (WBCs, CRP, and renal profile) as part of preoperative evaluation for appendicitis. Ultrasound was performed in 21.62% of the studies and CT scan in 32.24% of the studies. Accurate pain assessment in different age groups and development of effective postoperative treatment produces pain relief while speeding recovery and discharge without side effects of respiratory depression .
Preoperative patient counseling could lead to decreased LOS, cost reduction, and improve patient satisfaction. Physicians inform patients and families about the care process and expected outcomes as well as early ambulation, feeding, pain control, and discharge criteria . In this review, one article concluded that family counseling in the preoperative pathway for acute appendicitis to enhance early discharge policy .
4.1.3. Preoperative Antibiotics
Antibiotic prophylaxis is effective in prevention of postoperative complications in appendectomy patients regardless of the onset of administration . The Surgical Care Improvement Project recommended that initiation of antibiotics should be within one hour before surgical incision, patients should receive appropriate antibiotics for the procedure, and antibiotics should be discontinued within 24-hour post-surgery to reduce surgical side infection . Only 15 studies documented administration of antibiotics.
The duration of antibiotic treatment for complicated appendicitis had not been determined.
Studies on pediatric populations suggest that 3 or 5 days of postoperative antibiotics are associated with similar rates of complications. Antibiotics were stopped when certain criteria were achieved (i.e., no fever, normal WBC count, and resuming normal bowel function) . Limited literature has studied antibiotic guidelines for complicated appendicitis. A retrospective analysis of a sample of 410 subjects with complicated appendicitis found that there was no association between postoperative antibiotics and wound complication; however, postoperative antibiotics were associated with increased LOS .
4.2. Intraoperative Pathway Elements
4.2.1. Surgical Technique
There is lack of consensus on the most appropriate surgical technique for appendicitis management. In this review, studies indicated that 64.6% of appendicitis was managed by laparoscopic method. The first laparoscopic appendectomy (LA) was performed in 1981 by Semm. However, there was insufficient data to conclude that LA is superior to open technique . Where some studies have demonstrated reduction in postoperative pain, LOS, and wound infection with the laparoscopic approach, other studies have shown marginal or no clinical benefits, a higher rate of intra-abdominal and pelvic abscess, and increased cost     .
4.2.2. Intra-Abdominal Drain
In this review, two studies documented using intra-abdominal drains for their patients  . Emil et al. noted that peritoneal drainage is unnecessary in perforated appendicitis . In appendicitis cases performed on adults, the role of drain insertion differs based on whether the procedure is open or laparoscopic. Two systematic reviews concluded that routine abdominal drainage after open appendectomy for complicated appendicitis is not essential  . Cheng et al. found that there was no significant difference in the incidence rate of intra-peritoneal abscess between the groups of subjects with or without drain and abdominal drain might be associated with an increased LOS . Petrowsky et al. concluded that abdominal drain did not reduce postoperative complication and recommended that abdominal drain should be avoided at any stage of appendicitis management .
Historically, contaminated wounds were left open for delayed primary closure to decrease the risk of surgical site infection (SSI). A recent systematic review and meta-analysis of 8 articles, 5 of which assessed complicated appendicitis, showed that there was no significant difference between primary closure and delayed primary closure with a risk ration of 0.89 (95% CI: 0.46 - 1.73). Delayed primary closure had a significantly longer LOS than primary closure. However, findings were inconclusive due to the limited number of studies and a large-scale randomized clinical trial is required .
4.3. Postoperative Pathway Elements
Standardized discharge criteria are an essential clinical pathway element. Standardization should reduce variability among surgeons, enhance the efficacy of patient care, and reduce hospitalization cost given the significant morbidity and cost associated with advanced appendicitis treatment . This review found that 43.24% had a set of discharge criteria (Table 5). The majority of available literature assessed the efficacy of appendicitis protocol in discharging patients within 24 hours  . A matched case-control study with a sample size of 166 subjects investigated the effect of multidisciplinary discharge criteria protocol for uncomplicated appendicitis in children. The study found a reduction in median postoperative LOS by 29.2% and improved the rate of discharge within 24 hours from 12% - 24%; furthermore, the study concluded a total saving of 77,057 AUD .
Table 5. Discharge criteria.
Normal range is usually between 4000 and 11,000 per microliter of blood.
Findings of this review support literature findings that clinical pathway implementation leads to better outcomes . A retrospective study with a sample size of 580 subjects diagnosed with non-complicated appendicitis indicated a reduction in LOS from 40.1 - 23.5 hours and reduction in total cost per patient from $5783 - $4499 . Cundy et al. found that there was a 29.2% reduction in median postoperative LOS in protocol-based care, an improved rate of discharge within 24 hours, and a projected annual savings. Implementation of postoperative clinical pathway was significantly associated with positive clinical outcomes (P < 0.001) . In this review, 9 studies concluded that clinical pathway implementation is cost effective in managing patients with complicated and non-complicated appendicitis         . Nevertheless, 3 studies concluded that there was no significant impact of clinical pathway in reducing the cost of hospitalization for complicated appendicitis   .
4.4.1. Postoperative Complications
A systematic review and meta-analysis of 27 studies with a total sample size of 11,398 subjects with 19 different conditions found that the odds of reducing developing in-hospital complications are 0.58 when a clinical pathway was implemented . However, a prospective study in outpatient protocol for laparoscopic appendectomy showed no significant difference between complication rate between protocol and non-protocol groups .
Infection is the most common complication following appendectomy. It commonly occurred in patients with complicated appendicitis. Infection had a great impact on recovery time and quality of life. In this review, the reported rate of wound infection for non-complicated appendicitis was 0% - 7.5% and complicated appendicitis was 0.7% - 13%. Reviewed literature concluded that the rate of infection and abscess were less in the protocol group. These findings are consistent with findings from other studies that indicated clinical pathway implementation resulted in reduction of infection frequency.
4.5. Strengths and Limitations
The major strength of this review is that it is the first study to our knowledge to evaluate the available literature that assesses acute appendicitis clinical pathways. However, it was impossible to conduct a meta-analysis due to the nature of the study design of studies included in the review and the mode of data presentation.
The heterogeneity of studies included in this review was the main limitation. Another major limitation is related to the nature of study design; some studies involved multiple groups, and others were cross-sectional. Variation in treatment preference was another limitation.
Despite these limitations, findings of this review remain important to guide clinicians, surgeons and researchers in developing acute appendicitis management clinical pathway protocol.
Absence of a standardized clinical pathway for appendicitis management is challenging for clinicians and surgeons. The development of a standard clinical pathway is important to reduce complication rate, LOS, and cost, and to improve diagnostic efficacy. This review may serve as a foundation for the development of appendicitis guidelines.
The authors would like to thank Sophy George Joseph as well as Lesley Carson for the language editing of the manuscript.
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