Introduction

Acute appendicitis is one of the most common causes of acute abdominal pain, with an estimated lifetime risk of 8.6% for men and 6.7% for women [1, 2]. Although antibiotics have shown an increasingly important role in the treatment of acute appendicitis, appendectomy remains the gold standard in the treatment of acute appendicitis [3]. Previous evidence suggests that delayed surgery may increase the risk of complicated appendicitis [4,5,6]. Li et al. 's [7] meta-analysis suggests that delayed hospitalization or delayed surgery is associated with an increased risk of complicated appendicitis and complications. The 2020 guidelines [8] recommend immediate appendectomy. Hence, appendectomies are often performed as emergency operations [3]. However, whether performing an appendectomy at night affects the short-term outcome of appendicitis remains controversial.

Lack of sleep, disrupted circadian rhythms and long working hours can lead to cognitive and psychomotor declines and may increase the risk of medical errors [9, 10]. A retrospective study by Harriott et al. [11] suggests that nighttime surgery may increase conversion rates. However, Pogoreli´c et al. [3] found that the incidence of postoperative complications and conversion to laparotomy were similar between nighttime surgery and daytime surgery. In addition, systematic reviews and meta-analyses on this topic are still lacking.

Therefore, we conducted a systematic review and meta-analysis aimed at assessing whether surgery performed at night is associated with an increased risk of postoperative morbidity and mortality compared to daytime surgery in patients undergoing appendectomy.

Materials and methods

This meta-analysis was reported in accordance with the Preferred Reporting Items for Systematic Reviews and Meta-Analysis statement [12] and registered in the International Prospective Register of Systematic Reviews database (CRD42024538238) (Supplementary Tables S1).

Search strategy

Two authors independently (G.T. and J.W.) conducted a systematic and comprehensive literature search using the Embase, Web of Science, PubMed, and Cochrane Library databases to identify observational studies and RCTs published before March 26, 2024 (updated on July 1, 2024). Boolean operators (“AND”/ “OR”) and the “explode” function were used to construct a search string including the following keywords and MeSH (Medical Subjecting Headings): “night”, “nighttime”, “emergency”, “immediate”, “appendectomy”, “appendiceal resection”, “appendiceal surgery”, “appendectom*”, and “appendicectom*” (Supplementary Tables S2). In addition, we checked the reference lists of the identified articles and related reviews to further screen eligible studies. There were no language restrictions in the search.

Study selection

Trials included in this meta-analysis were chosen according to the patient, intervention, comparator, outcome, and study type (PICOS) criteria.

Patient: Patients undergoing appendectomy.

Intervention: Undergoing nighttime appendectomy.

Comparator: Undergoing daytime appendectomy.

Outcome: The main outcome measures were overall postoperative complications, mortality, intraoperative complications, reoperation, readmission, conversion to laparotomy, hospital stay and operation time.

Study type: RCTs, cohort studies, and case–control studies.

Exclusion criteria were as follows: Reviews, case reports, editorials, letters, and animal studies were excluded. To reduce the impact of delayed surgery as a confounding factor on our results, studies comparing immediate surgery at night and delayed evening surgery to daytime were excluded.

Data extraction

Data from all eligible studies were independently extracted by two reviewers (G.T. and J.W.) based on a previously established form, and any disagreements were resolved by discussion with a third-party independent reviewer (R.Z.). The main fields to be extracted included the author name, year of publication, country in which the study was conducted, study design, study population (sample size, age, and sex), outcomes (postoperative complications, mortality, intraoperative complications, reoperation, readmission, conversion to laparotomy, hospital stay and operation time). When data of interest in an article were unavailable, the corresponding author was contacted to obtain the necessary data.

Quality assessment

The risk of bias in the RCTs was assessed independently by two authors using the Cochrane risk-of-bias tool 2 [13]. The quality of the non-RCTs was assessed independently by two authors using the ROBINS-I tool [14]. To grade the quality of evidence, a GRADE assessment was performed through GRADEpro online tools (https://gradepro.org/). GRADE assessed the evidence as four levels: very low, low, medium, and high. Any discrepancy was resolved through discussion and intervention by a third reviewer whenever necessary.

Statistical analysis

The meta-analysis was performed using the Review 5.3 (The Nordic Cochrane Centre, The Cochrane Collaboration 2014; Copenhagen, Denmark) and Stata 15.1 (Stata Corp., College Station, TX, USA) softwares. Effect estimates are presented as the mean difference (MD) for continuous outcomes, and the odds ratios (ORs) for dichotomous outcomes, with 95% confidence intervals (CIs). Heterogeneity was assessed using the I2 statistic. When median, range, and/or interquartile range were reported in the studies together with the sample size, mean and standard deviation were estimated by following the methods described by Luo et al. [15] and Wan et al. [16] in order to be used for the pooled analysis. The random-effects model was used when there was significant heterogeneity with the I2 > 50%. Otherwise, the fixed-effects model was adopted [17]. Sensitivity analyses (one-study excluding method) were performed to assess the robustness of the main outcome measures. In addition, we used a random effects model for sensitivity analysis. Publication bias was assessed using the Egger’s test and funnel plot if 10 or more studies are identified. No subgroup analysis was performed in this study. Statistical significance was set at p < 0.05.

Results

Literature search results

The search strategy yielded 10,917 records, of which 3,424 duplicates were excluded. After excluding further 7,455 studies by reviewing the titles and abstracts, the full text of the remaining 38 studies was evaluated. Finally, 15 eligible studies [1,2,3, 11, 18,19,20,21,22,23,24,25,26,27,28] were included in the analysis (Fig. 1).

Fig. 1
figure 1

PRISMA flow diagram of the literature retrieval process

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Study characteristics and quality assessment

The main characteristics of the 15 included studies are shown in Table 1. The studies were published between 2010 and 2023 and included 33,596 participants (10,659 in the nighttime group and 22,937 in the daytime group). The number of participants per study ranged from 126 to 11,480. All included studies were retrospective cohort studies. Details of the quality evaluation are summarized in Supplementary Table S3. We evaluated the quality of evidence in this study (Supplementary Table S4). A part of the evidence (postoperative complications, mortality, reoperation, and readmission) were moderate, three (intraoperative complications, conversion to laparotomy and hospital stay) were low, one (operation time) was very low.

Table 1 Study Characteristics of the 15 included studies
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Main outcome measures

Postoperative complications

Fourteen studies [1,2,3, 11, 18,19,20,21,22,23,24, 26,27,28] reported data on overall postoperative complications. The point estimate suggested a 7% lower odds of postoperative complications in the night time appendectomy group, but 95% confidence intervals included no effect (OR 0.93, 95% CI 0.87, 1.00; I2 = 43%, P = 0.05). Heterogeneity between studies was low (Fig. 2) (Table 2).

Fig. 2
figure 2

Forest plots of overall postoperative complications between nighttime and daytime appendectomy

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Table 2 Summary of results from all outcomes
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Mortality

The effect of nighttime surgery on mortality has been reported in seven studies [1, 2, 11, 18, 24, 25, 27]. The point estimate suggested a 70% higher odds of postoperative mortality in the night time appendectomy group, but 95% confidence intervals included no effect (OR 1.70, 95% CI 0.37, 7.88, P = 0.50). No significant heterogeneity was observed between studies (I2 = 0%, P = 0.98). (Fig. 3).

Fig. 3
figure 3

Forest plots of mortality between nighttime and daytime appendectomy

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Intraoperative complications

Two studies [11, 18] described data on intraoperative complications. The point estimate suggested a 12% lower odds of intraoperative complications in the night time appendectomy group, but 95% confidence intervals included no effect (OR 0.88, 95% CI 0.08, 9.86; I2 = 62%, P = 0.11) (Fig. 4).

Fig. 4
figure 4

Forest plots of intraoperative complications between nighttime and daytime appendectomy

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Conversion to laparotomy

The effect of nighttime surgery on conversion to laparotomy has been reported in six studies [2, 3, 11, 18, 26, 27]. The point estimate suggested a 92% higher odds of conversion to laparotomy in the night time appendectomy group (OR 1.92, 95% CI 1.12, 3.29; I2 = 74%, P = 0.002) (Fig. 5).

Fig. 5
figure 5

Forest plots of conversion to laparotomy between nighttime and daytime appendectomy

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Reoperation

The association between nighttime surgery and reoperation was reported in three studies [3, 25, 27], and the point estimate suggested a 61% lower odds of reoperation in the night time appendectomy group, but 95% confidence intervals included no effect (OR 0.39, 95% CI 0.06, 2.55; I2 = 0%, P = 0.39) (Fig. 6).

Fig. 6
figure 6

Forest plots of reoperation between nighttime and daytime appendectomy

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Readmission

Five studies [1, 3, 11, 27, 28] described data on readmission rate. The point estimate suggested a 14% lower odds of readmission rate in the night time appendectomy group, but 95% confidence intervals included no effect (OR 0.86, 95% CI 0.65, 1.13; I2 = 0%, P = 0.57) (Fig. 7).

Fig. 7
figure 7

Forest plots of readmission between nighttime and daytime appendectomy

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Operation time

Six studies [1, 3, 11, 23, 26, 28] provided data on operation time. There was no significant difference in operation time between night surgery and day surgery (MD -0.06 min, 95% CI -5.67, 5.56; I2 = 97%, P < 0.00001) (Fig. 8).

Fig. 8
figure 8

Forest plots of operation time between nighttime and daytime appendectomy

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Hospital stay

Hospital stay was reported in eight studies [1,2,3, 11, 23, 26,27,28], and the length of hospital stay was comparable between night surgery and day surgery (MD -0.10 days, 95% CI -0.31, 0.12; I2 = 89%, P < 0.00001) (Fig. 9).

Fig. 9
figure 9

Forest plots of hospital stay between nighttime and daytime appendectomy

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Publication bias and sensitivity analysis

According to the funnel plots and Egger tests (Fig. 10), no publication bias was observed for the total postoperative complications. Sensitivity analysis showed that no single study affected the overall effect size of mortality, intraoperative complications, reoperation, readmission, operation time, hospital stay, and conversion to laparotomy. The effect size of overall postoperative complications changed when the study by Allaway et al. [20] (OR, 0.92; 95% CI, 0.86, 0.99, P = 0.02), Anderty et al. [21] (OR, 0.91; 95% CI, 0.85, 0.98, P = 0.02), or Harriot et al. [11] (OR, 0.93; 95% CI, 0.86, 0.99, P = 0.03) was excluded. The results of sensitivity analysis using a random effects model are summarized in Figure S1-S4.

Fig. 10
figure 10

Funnel plot of overall postoperative complications between nighttime and daytime appendectomy

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Discussion

To the best of our knowledge, this is the first meta-analysis to assess the impact of nighttime surgery on appendectomy outcomes. Our results suggest that appendectomy performed at night does not increase overall postoperative complications and mortality. In addition, the operation time, intraoperative complications, reoperation rate, readmission rate and length of stay were comparable to those of daytime surgery. However, the conversion rate for nighttime surgery was higher than daytime surgery.

Reducing morbidity and mortality after emergency surgery has been a major concern of emergency surgeons for decades [25]. Whether appendectomies should always be performed at night is controversial. Those who support night surgery argue that shorter preoperative delays may increase patient comfort, shorten hospital stays, lower hospital costs and reduce waste of medical resources [2, 3]. Especially in some centers with a large number of elective surgeries during the day, delaying emergency surgery may affect the normal development of elective surgery. Those who advocate delaying appendectomies until the day argue that a brief preoperative delay does not affect a patient's surgical outcome [28]. In addition, they are concerned that performing surgery at night may increase the risk of making mistakes due to the fatigue of the surgeon, thus increasing the postoperative morbidity of patients [28]. The effect of nighttime surgery on different surgical procedures is different. Several studies have shown that nighttime surgery with type A aortic dissection, supracondylar humeral fractures, and colorectal is associated with an increased risk of morbidity and mortality [29,30,31]. However, Ndegbu et al. 's [25] study found that non-complicated emergency surgeries performed at night, such as appendectomy, enterectomy, and intestinal perforation closure, had similar outcomes to those performed during the daytime. in addition, a recently published meta-analysis [32] suggests that out-of-hours (in the evenings, at night, or on weekends) surgery does not increase the risk of postoperative morbidity and mortality from cholecystectomy. Similarly, our study found no increase in complications, mortality, or reoperation when appendectomies were performed at night. In addition, the incidence of intraoperative complications did not differ significantly between the nighttime surgery group and the daytime surgery group. A retrospective study by Tago et al. [33] also showed that, compared with appendectomy performed at night, delaying appendectomy to the daytime did not increase the incidence of postoperative complications. All these evidences support that nighttime surgery does not compromise the outcome of appendectomy.

Although an appendectomy is a relatively quick surgical procedure, prolonged surgery can prolong hospital stays and increase the risk of postoperative complications and readmissions [27, 34]. Therefore, operation time remains an important indicator to evaluate the effect of nighttime surgery on appendectomy [27]. The results of this meta-analysis suggested that nighttime surgery was shorter than daytime surgery, but there was no statistical difference. The study by Tomasko et al. [35] found that despite the increased workload and sleepiness during night shifts, clinicians were still able to perform operations proficiently and other staff members were able to perform tasks correctly. This suggests that performing an appendectomy at night does not affect the efficiency of appendectomy [27]. In addition, in terms of postoperative recovery, our results suggest that the length of postoperative hospital stay for nighttime surgery is comparable to that for daytime surgery. None of the studies we included provided data on hospitalization costs. However, this is a topic worthy of further discussion, and it is necessary to conduct economic evaluation on this topic in the future.

Compared with open surgery, laparoscopic appendectomy has the advantages of less adverse reactions, shorter operation time and hospital stay, fewer complications, and low inflammatory reaction, and has been widely used in the treatment of acute appendicitis [36]. In some complicated cases, the surgeon may consider switching to open surgery when the appendix and surrounding anatomy are difficult during the operation [37]. Previous literature suggests that risk factors for conversion to laparotomy include age > 13 years, male, obesity, appendicitis with perforation, or diffuse peritonitis [3]. Our study suggests that the conversion rate of operation during nighttime is higher than that during daytime. However, the increased rate of conversion to laparotomy did not seem to affect the outcome of appendectomy. Postoperative morbidity, mortality, reoperation rates, readmission rates, and length of stay were comparable in the nighttime and daytime surgery groups. In addition, whether the increase in conversion rates is related to fatigue and increased workload among on-duty physicians is unclear. Results from several studies [3, 38] suggest that surgeon fatigue does not appear to be associated with poorer surgical outcomes. The increase in conversion rates may be related to the higher proportion of complicated cases at night, as sicker patients cannot wait until the day to come to the hospital [3, 25]. In a retrospective analysis of data on 855,694 appendectomies performed in Germany between 2010 and 2021, Uttinger et al. [39] found that the incidence of complicated appendicitis was 27.6%, which increased to 30% in patients undergoing nighttime surgery. Therefore, it is necessary to conduct adequate preoperative evaluation when performing appendectomy at night, identify complicated cases as much as possible, and develop appropriate surgical strategies to reduce the occurrence of conversion to laparotomy.

Our study has the following strengths. On the one hand, we conducted a comprehensive literature search to reduce potential bias. On the other hand, advanced statistical methods (sensitivity analysis and publication bias) were used to further confirm the reliability of our results.

However, our study has several limitations. First, all the studies we included were retrospective studies and suffered from the inherent flaws (selection bias and residual confounding) of retrospective studies. Second, some of our outcomes were highly heterogeneous, but due to the limited number of included studies, further subgroup analysis was not possible. In addition, heterogeneity in outcome reporting which precluded inclusion of most studies in secondary outcome meta analyses. Finally, different studies have different definitions of nighttime surgery, such as some studies defining nighttime surgery as 8 p.m. to 8 a.m., and some studies defining it as 10 p.m. to 8 a.m. In addition, the severity of appendicitis at admission may affect whether surgery is performed as quickly as possible, so future studies need to consider the impact of these factors and use statistical methods to balance them.

In conclusion, based on current evidence, our results suggest that appendectomy performed at night is safe, with postoperative complication rates and mortality comparable to those of daytime surgery. To avoid unnecessary surgical delays, night surgery is still a viable and even necessary option. However, it is important to note that night surgery is associated with a higher rate of conversion to open surgery, which means that surgeons should fully evaluate the patient's condition when choosing a surgical strategy (laparoscopy or open surgery) at night. In addition, given the methodological limitations of the included studies, the results of this study need to be validated by high-quality prospective studies.