DOI: https://doi.org/10.21203/rs.3.rs-18722/v1
Background:Even though many studies have reported comparisons of the lateral transperitoneal adrenalectomy (LTA)and posterior retroperitoneal adrenalectomy (PRA) approaches,the conclusions were inconsistent.This meta-analysis aims at a systematic assessment of LTA and PRA.
Methods:We searched MEDLINE, Pubmed, and Embase database and finally obtained 19 studies published since January 2009.Systematic review was conducted based on the Preferred Reporting Items for Systematic Reviews and Meta-analyses. RevMan 5.3(Cochrane Collaboration) was used for data analysis.
Results:19 studies were included in the meta-analysis.The clinical characteristics of the 2 groups were similar(age, BMI, proportion of right sided, proportion of bilateral lesions,and previous abdominal surgery).There was slightly higher heterogeneity in proportion of male patients (OR 0.87, 95% CI 0.78 to 0.97, P = 0.01) and size of the tumor (MD 0.62, 95% CI 0.16 to 1.08, P = 0.008).The results confirmed that the PRA group was superior to LTA group regarding shorter operative time (MD 17.54, 95% CI 9.67 to 25.40, P < 0.0001),lower estimated blood loss (MD 37.75, 95% CI 18.08 to 57.41, P = 0.0002), shorter hospital stay (MD 1.19, 95% CI 0.76 to 1.63, P < 0.00001) and shorter time to first oral intake(MD 0.48, 95% CI 0.11 to 0.86, P =0.01).There were no statistically significant differences between LTA and PRA regarding overall complication(OR 1.37, 95% CI 0.96 to 1.97, P = 0.08),conversion to open laparotomy (OR 1.16, 95% CI 0.63 to 2.16, P = 0.63) or blood transfusion(OR 2.22, 95% CI 0.51 to 9.57, P = 0.28) .
Conclusion:This meta-analysis suggests that PRA has more advantages over LTA,such as shorter operative time,lower estimated blood loss,shorter hospital stay and shorter time to first oral intake.And there were no statistically significance between LTA and PRA in terms of postoperative outcomes(total complications, conversion rates and blood transfusion).
In the last decades,adrenalectomy has progressed from an operation to minimally invasive surgery[1].Some patients require surgical treatment because of functional or suspected malignancy adrenal tumors [2]. Laparoscopic adrenalectomy is the preferred approach for removal of most adrenal tumors.Various studies demonstrated the safety and efficacy of laparoscopic technique.Among laparoscopic approaches,the lateral transperitoneal adrenalectomy (LTA) and the posterior retroperitoneal adrenalectomy (PRA) are common surgical procedures for the treatment of adrenal tumors.
Since first reported in 1992[3], LTA have been widely increased. LTA offers a wide working space for removal of larger adrenal tumors[4]. Conversely, PRA, first reported in 1995,can provides direct access to the adrenal tumor and avoids potential injury to the intra-abdominal organs.[5] Moreover, in PRA, adhesions can be avoided in patients with previous abdominal interventions, and the surgeon can treat bilateral tumors simultaneously, without changing position[6]. Currently, selection of surgical modalities for adrenal require a comprehensive consideration of the experience of surgeon,anatomical location and size of tumor[7].
Even though many studies have reported comparisons of the two laparoscopic approaches,the conclusions were inconsistent.This meta-analysis aims at a systematic assessment of LTA and PRA.
Data sources and search
We searched MEDLINE, Pubmed, and Embase database and finally obtained 19 studies published since January 2009.Systematic review was conducted based on the Preferred Reporting Items for Systematic Reviews and Meta-analyses. The following keywords were used:“transperitoneal”,“retroperitoneal”,and “adrenalectomy”. We also conducted a manual search for related articles from references to identify additional articles. All studies were extracted by two authors separately, and any divergence was resolved through consensus.
Selection criteria
Inclusion criteria were: (1) Comparison of clinical characteristics and perioperative outcomes of patients with LTA and PRA;(2) studies having full-text and relevant data were included;(3)studies published in English language;(4)All included studies provide the following data: basic characteristics of patients (age, gender [Male/ Female] ,body mass index [BMI], previous abdominal surgery), characteristics of tumor (size, side, and type of endocrine disorder), surgical outcomes (operative time, blood loss, time to oral intake, and duration of hospital stay), and postoperative outcomes (total complications, conversion, blood transfusion and mortality). The flow chart of study selection is shown in Figure1.The meta-analyses were based on published researches,so ethical approval was not required for our study.
Quality assessment
As shown in Figure 2 and Figure 3,Cochrane 'Risk of bias' assessment tool was used for quality assessment in this meta-analysis.Evaluation based on:A:Sequence generation;B:Allocation concealment;C: Blinding of participants,personnel;D: Blinding of outcome assessment;E:Incomplete outcome data;F:Selective reporting;G: Other sources of bias.All authors were involved in the quality assessment of articles included, and any divergence was resolved through consensus.Finally everyone agreed on the quality assessment.
Statistical analyses
RevMan 5.3(Cochrane Collaboration)[8] was used for data analysis.Variables were pooled only when more than 3 studies were evaluated.The odds ratio(OR) and the corresponding 95% confidence interval [CI] [8] were used to assess the differences. We considered the study present significant heterogeneity if P<0.05.Statistical heterogeneity was measured with the I2 statistic.The random-effects model was used when I2>50%.
If original articles did not provide means and standard deviations (SDs) or we did not get the data we needed from authors, we used median, range, and sample size to estimate the means and SDs[9].
Study Characteristics
Of 592 retrieved studies, 573 articles were excluded for different reasons.Finally, 19 studies [10-28] were included in our analysis.Table 1 lists the basic characteristics of the included studies in the meta-analysis,and Table 2 shows the clinical and pathologic characteristics of the included studies.The two groups were similar in age (MD -4.03, 95% CI -8.82 to 0.76, P = 0.10), BMI (MD 0.17, 95% CI -0.53 to 0.87, P = 0.64), proportion of right sided (OR 0.91, 95% CI 0.74 to 1.12, P = 0.35), proportion of bilateral lesions (OR 1.21, 95% CI 0.52 to 2.80, P = 0.65),and previous abdominal surgery (OR 0.91, 95% CI 0.59 to 1.43, P = 0.70),as shown in Fig.4A-E.
The heterogeneity between the two groups was slightly higher in proportion of male patients (OR 0.87, 95% CI 0.78 to 0.97, P = 0.01)(Fig.4F);in addition,the tumor in the PRA group was slightly smaller (MD 0.62, 95% CI 0.16 to 1.08, P = 0.008) (Fig.4G).
The pathologic characteristics of patients(Cushing’s syndrome (OR 1.16, 95% CI 0.79 to 1.71,P = 0.46), primary aldosteronism (OR 0.67, 95% CI 0.47 to 0.94,P = 0.02), pheochromocytoma (OR 1.09, 95% CI 0.79 to 1.51,P = 0.59), and nonfunctioning tumor (OR 1.05, 95% CI 0.75 to 1.48,P = 0.76)) and proportion of malignant tumor (OR 1.11, 95% CI 0.64 to 1.92,P = 0.72) are shown in Table 3 (Fig7A-E).
Comparison of surgical outcomes between LTA and PRA
Operative time
18 studies including 1663 patients were pooled to evaluate operative time. The heterogeneity among studies was high(P <0.00001, I2 = 95%).The PRA group was associated with a significantly shorter operative time (MD 17.54, 95% CI 9.67to 25.40, P < 0.0001) (Fig.5A).
Blood loss
14 studies including 1168 patients were pooled to evaluate blood loss.Significant heterogeneity was shown among studies (P<0.00001, I2 = 97%). The results showed greater estimated blood loss in the LTA group with a random-effects model(MD 37.75, 95% CI 18.08 to 57.41, P = 0.0002) (Fig.5B).
Hospital stay
16 studies including 1466 patients were pooled to evaluate hospital stay. Length of hospital stay was significantly less in the PRA group (MD 1.19, 95% CI 0.76 to 1.63, P < 0.00001) (Fig.5C).
Time to first oral intake
6 studies including 521 patients were pooled to evaluate time to first oral intake. The results showed a significantly shorter time to first oral intake in the PRA group(MD 0.48, 95% CI 0.11 to 0.86, P =0.01) (Fig.5D).
Postoperative outcomes
Results of postoperative complications were shown in Table 3.There was no statistical significance between LTA and PRA for overall complication(OR 1.37, 95% CI 0.96 to 1.97, P = 0.08) (Fig.6A) ,conversion to open laparotomy(OR 1.16, 95% CI 0.63 to 2.16, P = 0.63) (Fig.6B) or blood transfusion(OR 2.22, 95% CI 0.51 to 9.57, P = 0.28) (Fig.6C). Only Two patients in the LTA group (Berber et al19) died postoperatively from cardiac and pulmonary causes. No mortality was encountered in PRA group.
Laparoscopic adrenalectomy has become an accepted surgical procedure world wide for adrenal gland disease.Despite LTA has advantages of wide surgical space and familiarity of anatomy,PRA are equally effective and safe because of the superiority of direct approach to adrenal lesions[6,21,22].Besides,PRA,which can avoid injury to abdominal organs[29] ,perhaps should be preferred for patients with a history of abdominal surgery and in bilateral adrenal lesions.
Although numerous reports have identified PRA seems more desirable compared with LTA,most of them have the disadvantage of small sample size or stringent inclusion criteria in a single-institution. To overcome these limitations, we performed this meta-analysis.Although no difference was shown in most clinical characteristics (age, BMI, proportion of right sided, proportion of bilateral lesions,and previous abdominal surgery),the heterogeneity was found in the proportion of male patients and size of the tumor between 2 groups. Both procedures were confirmed the safety and efficacy.The results showed PRA has more advantages over LTA,such as shorter operative time ,lower estimated blood loss,shorter hospital stay and shorter time to first oral intake.The meta-analysis showed that there were no statistically significance between LTA and PRA in terms of postoperative outcomes( total complications, conversion rates and blood transfusion).
Rates of conversion to laparotomy of LTA and PRA were 3.1% (23/753) and 2.6% (16/614), respectively.And the reasons for conversion were different. Conversion occurred in LTA due to the large tumor (which could not be separated safely from the undersurface of the liver laparoscopically), extensive adhesions from prior abdominal surgery,and malignancy with renal vasculature;Whereas the reason of conversion in RLA are uncontrolled bleeding, adhesions by intraoperatively suspected malignant pheochromocytoma ,secondary adrenal metastases with invasion, a large primary tumor and inadequate visualization, BMI of 40 had failure to progress, and inability to maintain adequate retroperitoneal insufflation due to a small tear in the peritoneum.
Complications occurred in both groups. The reported complications in LTA included episode of postoperative pneumonia,symptomatic port-site incisional hernia, colon injury,spleen injury,a pulmonary embolism,symptomatic atrial fibrillation, pneumothorax, and hematoma.The complication in RLA included neuromuscular pain (which was temporary in most patients),peritoneum injury,pleura injury, retroperitoneal hematoma, permanent blindness(unexplained thromboembolism to the retinal artery).
There were certain limitations in our analysis:the 10-year study may results in the risk of potential confounding variables and biases.In addition,the higher heterogeneity was found in the size of the tumor ,which demonstrate PRA perhaps superior in smaller tumours. Further studies are needed to confirm the results of larger adrenal tumors.
This meta-analysis suggests that PRA has more advantages over LTA,such as shorter operative time,lower estimated blood loss,shorter hospital stay and shorter time to first oral intake.And there were no statistically significance between LTA and PRA in terms of postoperative outcomes(total complications, conversion rates and blood transfusion).
LTA:lateral transperitoneal adrenalectomy; PRA: posterior retroperitoneal adrenalectomy BMI:body mass inde ;MD:Mean difference;OR:odds ratio;SD:standard deviation; CI:confidence interval;CT:computed tomography;NA:not available
Ethics approval and consent to participate
All analyses were based on previous published studies, thus no ethical approval and patient consent are required.
Consent for publication
Not applicable.
Availability of data and materials
The datasets used and/or analysed during the current study available from the corresponding author on reasonable request.
Competing interests
The authors declare that they have no competing interests.
Funding
LYY, LQ, and LL performed the data extraction, carried out the meta-analysis and drafted the paper.LYY was funded by Natural Science Foundation of Shandong Province(ZR2017LH016), Yantai Science and Technology Bureau(2018SFGY117).
The funding agencies had no role in this meta-analysis.
Authors’contributions
WHT designed the research, interpreted the data and revised the paper. LYY, LQ, and LL performed the data extraction,data analysis and review of drafts. All authors read and approved the final manuscript.
Acknowledgements
Not applicable.
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Table 1.Characteristics of the included studies
Author |
Year |
Country |
Type of study |
Trial period |
Inclusion criteria |
Exclusion criteria |
Sample |
|
LTA |
PRA |
|||||||
Kozlowski et al10 |
2019 |
Poland |
Prospective randomized |
2015.2-2018.6 |
size of the adrenal tumor for planned unilateral adrenalectomy up to 8 cm |
tumors > 8 cm, imaging features suggesting primary invasive malignant tumors and refusal of the patient to undergo randomization |
33 |
44 |
Chai et al11 |
2019 |
Korea |
Prospective randomized |
2012.9-2016.2 |
unilateral benign tumor,BMI≤35kg/m2,age≥18 and age<80,tumor size<7cm in maximal diameter on preoperative CT scan (<5cm for pheochromocytoma),no history of abdominal surgery in the same quadrant of adrenal tumor location, and normal cognitive function. |
necessity of additional surgical procedure,pregnancy,ongoing infection,uncontrolled hypertension,or a history of coronary heart disease (CHD), or cerebrovascular disease (CVD) |
42 |
41 |
Shiraishi et al12 |
2019 |
Japan |
Retrospective, non-randomized |
2008.1-2017.12 |
Pheochromocytomas > 5cm |
Not specified |
12 |
10 |
WeiChen et al13 |
2018 |
China |
retrospective |
2011.1-2015.6 |
(i) the patient was confirmed as having an adrenal tumor by imaging examination and underwent minimally invasive surgery treatment, (ii) the baseline indicators and perioperative parameters were completely recorded, and (iii) a large adrenal tumor was defined as an adrenal tumor with a diameter larger than 5 cm. |
(i) there were no measurable data reported, (ii) the tumor was operated on via open surgery, and (iii) a hand-assisted laparoscopic method was adopted during the surgery.
|
37 |
41 |
Vorselaars et al14 |
2018 |
Europe, America, Canada |
Retrospective non-randomized |
2000-2016 |
All consecutive patients with pheochromocytoma who underwent unilateral laparoscopic adrenalectomy |
patients with open,partial,bilateral,or converted procedures |
240 |
101 |
Marek-Safiejko et al15 |
2016 |
Poland |
retrospective |
2010.2-2015.2 |
Not specified |
All patients with suspected adrenal carcinoma or a tumor larger than 10 cm were qualified for the conventional method |
27 |
77 |
Lairmore et al16 |
2016 |
Thailand |
retrospective |
2005.1-2015.4 |
Not specified |
Primary malignant adrenal tumors, and tumors not felt to be amenable to a minimally invasive approach (generally>8.0cm) were excluded. |
67 |
76 |
Chiang et al17 |
2015 |
Taiwan |
Retrospective, nonrandomized |
2000.3-2011.9 |
Not specified |
Adrenocortical malignancies were excluded |
24 |
31 |
Barczynski et al18 |
2014 |
Poland |
Prospective, randomized |
2006.1-2008.6 |
unilateral adrenal surgery for a benign tumor up to 7 cm in diameter |
diffuse peritonitis in history, major abdominal surgery in history, planned bilateral adrenal surgery, adrenal tumor more than 7cm in diameter,suspected adrenocortical cancer, metastasis to adrenal gland,previous adrenal surgery, pregnancy or lactation, age less than 18 or more than 80 years,American Society of Anesthesiologists fitness grade IV, and inability to comply with the follow-up protocol |
32 |
33 |
Cabalag et al19 |
2014 |
Australia |
Retrospective Nonrandomized |
2009.10-2011.12 |
functional tumors <8cm without signs of local invasion, nonfunctional tumors between 4 and 8cm, or<4cm with suspicious features on preoperative imaging,and solitary metastasis to the adrenal. |
Not specified |
13 |
10 |
Mohammadi-Fallah et al20 |
2013 |
Iran |
Prospective, randomized |
2008.9-2011.11 |
Not specified |
patients with morbid obesity (BMI>40kg/m2), prior major abdominal surgery,clinical suspicion of malignancy,tumor size>6cm,and bilateral adrenalectomy |
11 |
13 |
Constantinides et al21 |
2013 |
UK |
prospectively |
2010.9-2012.9 |
All adult patients undergoing unilateral adrenalectomy via a minimally invasive approach were eligible for inclusion in the study irrespective of surgical indication |
Patients undergoing open adrenalectomy, bilateral adrenal surgery,or paraganglioma resection were excluded |
36 |
35 |
Lee,CR et al22 |
2012 |
Not specified |
retrospective |
2009.1-2010.7 |
Not specified |
bilateral pheochromocytoma |
26 |
17 |
Miccoli et al23 |
2011 |
Italy Germany
|
retrospective |
1994-2008 |
underwent bilateral synchronous adrenalectomy |
Not specified |
20 |
14 |
Ramacciato et al24 |
2011 |
Italy |
nonrandomized, retrospective |
1995-2009 |
Not specified |
Not specified |
127 |
44 |
Kiriakopoulos et al 25 |
2011 |
Greece |
Prospective nonrandomized |
2008.5-2010.9 |
Not specified |
Not specified |
30 |
30 |
Dickson et al26 |
2011 |
America |
retrospectively |
2000.5-2009.12 |
Not specified |
Not specified |
23 |
23 |
Li,QY et al27 |
2010 |
China |
retrospective |
1999-2008 |
unilateral benign pheochromocytoma<6cm in diameter have undergone LA for pheochromocytoma |
Patients with bilateral pheochromocytoma or malignancy |
40 |
59 |
Berber et al28 |
2009 |
America |
retrospective |
1994-2008 |
Not specified |
Not specified |
69 |
90 |
Total |
|
|
|
|
|
|
909 |
789 |
LTA:lateral transperitoneal adrenalectomy;PRA:posterior retroperitoneoscopic adrenalectomy.CT:computed tomography
Table 2.Clinical characteristics
Study |
Group |
Tumor size ,cm (±SD) |
Age, mean years (±SD) |
BMI,kg/m2 (±SD) |
Gender (Male /female) |
Tumor location (Right/Left /Bilateral) |
Type of endocrine disorder |
|||||
Pheocromocytoma |
Malignant |
Conn’s disease |
Cushing syndrome |
Nonfunctioning |
Others |
|||||||
Kozlowski et al10 |
LTA PRA |
4.1* 4.0* |
61.2±8.3 59.3±10.2 |
30.1±6 29.1±5.2 |
13/20 21/23 |
11/22/0 18/26/0 |
4 9 |
1 3 |
2 4 |
5 3 |
22 28 |
0 0 |
Chai et al11 |
LTA PRA |
2.9±1.4 3.0±1.3 |
48.0±11.4 46.4±11.0 |
24.2±3.3 23.6±3.0 |
14/28 15/26 |
18/24/0 18/23/0 |
8 7 |
NA |
20# 16# |
7 10 |
7 8 |
0 0 |
Shiraishi et al12 |
LTA PRA |
6.6* 7.4* |
58.8* 56.3* |
23.4* 23.2* |
7/5 4/6 |
7/5/0 6/4/0 |
12 10 |
NA |
0 0 |
0 0 |
0 0 |
0 0 |
WeiChen et al13 |
LTA PRA |
5.76±1.34 5.81±1.17 |
47.92±29.61 44.41±38.90 |
23.60±2.92 23.52±2.46 |
23/14 26/15 |
10/25/2 11/29/1 |
3 5 |
4 2 |
20 18 |
NA |
NA |
10 16 |
Vorselaars et al 14 |
LTA PRA |
4.52±1.94 3.4±1.9 |
5.5±15.4 45.3±17.0 |
25.3±5.3 24.0±3.6 |
102/138 46/55 |
130/110/0 45/56/0 |
240 101 |
NA |
0 0 |
0 0 |
NA |
0 0 |
Marek-Safiejko et al15 |
LTA PRA |
6.1±2.1 4.6±1.4 |
53.6±11.5 58.8±10.4 |
28.8±4.9 30.4±3.8 |
11/16 32/45 |
12/15/0 39/38/0 |
5 16 |
4 4 |
1 10 |
4 7 |
17 44 |
0 0 |
Lairmore et al16 |
LTA PRA |
3.6±2.1 2.38±1.2 |
53.5* 52.9* |
32.67* 31.23* |
23/43 36/36 |
29/38/0 36/40/0 |
NA |
NA |
NA |
NA |
NA |
NA |
Chiang et al17 |
LTA PRA |
4.6±0.82 3.5±1.56 |
53.3* 53.15* |
25.41* 25.07* |
11/13 17/14 |
24/0/0 31/0/0 |
3 5 |
NA |
8 12 |
0 2 |
10 11 |
3 1 |
Barczynski et al18 |
LTA PRA |
4.03* 3.93* |
46.6* 47.9* |
27.3* 27.6* |
9/23 8/25 |
15/17/0 16/17/0 |
7 8 |
NA |
7 7 |
3 4 |
15 14 |
0 0 |
Cabalag et al19 |
LTA PRA |
3.2* 3.5* |
47* 61* |
28* 28.9* |
5/8 5/5 |
4/9/0 5/5/0 |
NA |
0 1 |
NA |
NA |
NA |
NA |
Mohammadi-Fallah et al20 |
LTA PRA |
2.92* 2.63* |
42.9* 42.23* |
26,72* 27.46* |
5/6 5/8 |
6/5/0 8/5/0 |
2 2 |
NA |
2# 1# |
3 4 |
4 6 |
0 0 |
Constantinides et al21 |
LTA PRA |
4.1±2.31 2.83±1.27 |
49.52±13.62 49.1±13.55 |
26.8±4.64 29.8±5.52 |
15/21 13/22 |
18/18/0 19/16/0 |
7 7 |
0 0
|
10 10 |
8 5 |
4 9 |
7 4 |
Lee,CR et al22 |
LTA PRA |
3.86±3.83 2.64±1.61 |
53.4±9.9 57.4±13.9 |
24.49±2.61 24.99±3.18 |
7/19 6/11 |
7/18/1 8/9/0 |
8 2 |
NA |
4# 7# |
3 2 |
11 6 |
0 0 |
Miccoli et al23 |
LTA
PRA |
L64.06* R61.1* L37.4* R42.8* |
48.1*
38.9* |
29.4*
26.3* |
7/13
6/8 |
0/0/20
0/0/14 |
4
7 |
NA |
0
1 |
16
5 |
NA
|
0
1 |
Ramacciato et al24 |
LTA PRA |
4.4±2.8 4.8±1.9 |
51.8±14.0 54.3±12.5 |
NA |
52/75 28/16 |
63/58/6 31/13/0 |
20 8 |
14 5 |
NA |
NA |
NA |
93 31 |
Kiriakopoulos et al25 |
LTA PRA |
4.9* 3.8* |
49.5* 53.0* |
NA NA |
11/19 9/21 |
16/14/0 10/20/0 |
6 6 |
2 2 |
4# 4# |
18 17 |
NA |
0 1 |
Dickson,PV et al26 |
LTA PRA |
4.0±2.2 3.3±1.8 |
42.0±18.1 47.3±16.1 |
26.1±5.4 26.2±6.6 |
7/16 11/12 |
9/13/1 11/12/0 |
NA |
NA |
NA |
NA |
NA |
NA |
Li,QY et al27 |
LTA PRA |
4.5±0.5 4.3±0.8 |
37.51±5.12 36.74±4.32 |
25.5±5.78 26.31±6.22 |
17/23 25/34 |
22/18/0 34/25/0 |
NA |
NA |
NA |
NA |
NA |
NA |
Berber et al28 |
LTA PRA |
4.4±0.3 2.8±0.1 |
52±14 51±14 |
32±9 28±6 |
25/44 43/47 |
27/38/4 38/43/9 |
23 12 |
7 10 |
3 31 |
9 15 |
18 20 |
9 2 |
*except median.# aldosteronism
NA:not available.
Table 3.Clinical characteristics and postoperative outcomes
Variable |
N |
OR |
95% CI |
P value |
Type of endocrine disorder Pheocromocytoma |
15 |
1.09 |
0.79 to 1.51 |
0.59 |
Conn’s disease |
14 |
0.67 |
0.47 to 0.94 |
0.02 |
Cushing syndrome |
11 |
1.16 |
0.79 to 1.71 |
0.46 |
Nonfunctioning |
9 |
1.05 |
0.75 to 1.48 |
0.76 |
Malignant |
7 |
1.11 |
0.64 to 1.92 |
0.72 |
Total complications |
14 |
1.37 |
0.96 to 1.97 |
0.08 |
Conversion to open rates |
14 |
1.16 |
0.63 to 2.16 |
0.63 |
Blood transfusion |
7 |
2.22 |
0.51 to 9.57 |
0.28 |
CI, Confidence interval; N, number of studies reporting the variable; OR, odds ratio.