Effect of perioperative blood transfusion on complications following emergency non-trauma laparotomy in Mulago hospital: A prospective cohort study.

doi:10.21203/rs.3.rs-3719401/v2

Background: Blood transfusion may be required in the management of patients undergoing emergency non-trauma laparotomy. However, several retrospective cohort studies involving patients undergoing laparotomy for benign and malignant indications have identified blood transfusion as a significant predictor of postoperative infections and mortality. Still, no study has explored such an association in our setting. We aimed to determine the effect of perioperative blood transfusion on the 30-day risk of surgical site infections and mortality among patients undergoing emergency non-trauma laparotomy in a large urban tertiary hospital in a low-resource setting.

Methods: In this prospective cohort study, we recruited 160 adult patients admitted to the general surgery wards 48 hours after emergency non-trauma laparotomy. We grouped them based on transfusion exposure and non-exposure. Independent variables, including perioperative blood transfusion and confounders, were recorded on entry, while dependent variables, including the presence or absence of surgical site infection and mortality, were obtained over a 30-day follow-up period. Data were analysed using EPI INFO version 7, SPSS version 29 & Stata version 14.

Results: All 160 participants recruited, 28 (17.5%) transfused (exposed) and 132 (82.5%) not transfused (non-exposed), were included in the final analysis. Transfusion exposure (RR, 7.81; 95% CI, 2.58 – 23.63; p=0.0003) and preoperative leucocytosis/leucopoenia (RR, 2.19; 95% CI, 1.04 – 4.65; p=0.040) were identified as independent risk factors for SSI after multivariate logistic regression analysis adjusted for confounders including preoperative anaemia, young-to-middle-aged adults, cloudy/purulent/feculent exudate, gut perforation diagnosis, female sex, and registrar-led surgical team. Furthermore, transfusion exposure (HR, 3.36; 95% CI, 1.11 – 10.25; p=0.033) and old age (HR, 5.50; 95% CI, 1.67 – 18.11; p=0.005) were identified as independent risk factors for 30-day mortality after multivariate Cox regression analysis adjusted for confounders including high ASA score, immunodeficiency, cloudy/purulent/feculent exudate, bowel obstruction and high-risk procedure for bowel leak.

Conclusion: Among patients undergoing emergency non-trauma laparotomy, perioperative blood transfusion compared to no perioperative blood transfusion increased the risk of 30-day SSI by 7.81 and the 30-day mortality risk by 3.36. A restrictive transfusion strategy and a more extensive multicentre prospective cohort study are recommended.

Perioperative Blood Transfusion

Surgical Site Infection

Mortality

Emergency Non-Trauma Laparotomy

Perioperative blood transfusion is often required in the management of anaemia in patients undergoing laparotomy. It improves oxygen-carrying capacity and hence is life-saving, especially in cases of ongoing trauma-related or intravascular coagulopathy-related haemorrhage.

However, blood transfusion is associated with several complications, including postoperative infection due to transfusion-related immunomodulation (TRIM) and infection (bacterial/viral) transmission, among others (1)(2). This is illustrated by numerous retrospective cohort studies in high-income countries that have identified perioperative allogeneic blood transfusion as a predictor of postoperative infection and mortality in patient populations. They include patient populations such as major emergency abdominal surgery (unadjusted 30-day serious complication rate or Clavien-Dindo score ≥ 3a: 60.1% vs. 28.1%, p<0.001; adjusted 30-day mortality following RBC/fresh frozen plasma/platelet transfusion: HR, 4.1; CI, 2.5-6.8; p<0.001) (3); colorectal cancer surgery (mortality: 41.33% vs. 7.64%; HR, 2.747; 95% CI, 1.048–7.205) (4); (poor survival: HR, 3.18; 95% CI, 2.08–4.84) (5), and Crohn’s disease (SSI rate: 28.3% vs 14.4%; OR, 2.2; 95% CI, 1.8–2.7; p<0.001) (6).

In Uganda, surgical site infection (20%) and mortality within 30 days (15.6%) are among the most common post-laparotomy complications (7), and in this setting, emergency laparotomy constitutes 67.1% of laparotomies (8). It is worth noting that emergency laparotomies are frequently conducted with little patient preparation, hence often resulting in more postoperative complications than elective laparotomy (33.7% vs 14.2%, p<0.05) (9). Although approximately one (1) in every five (5) patients undergoing emergency non-trauma laparotomy in this hospital receives a blood transfusion (unpublished data, Egbe FE, 2022), no study has explored the association between perioperative blood transfusion and postoperative complications in this setting.

This study aimed to assess the association between perioperative blood transfusion and 30-day risk of surgical site infection and mortality among patients undergoing emergency laparotomy for gut perforation and bowel obstruction in Mulago National Referral Hospital, a large urban tertiary hospital in Uganda. Exploring this association in this low-income setting, where blood supply is limited compared to demand, may inform blood transfusion policies and strategies among emergency non-trauma laparotomy patients in Uganda and similar low-income settings.

Study Design and Setting

This prospective cohort study was conducted over 26 weeks between February 17, 2023, and August 17, 2023, at the Mulago National Referral Hospital. It is the teaching hospital of the College of Health Sciences, Makerere University, and Uganda's main public referral hospital. It serves several regional referral hospitals and other lower-level referral health facilities in Uganda and neighbouring countries, including South Sudan and the Democratic Republic of the Congo. This institution's high influx of patients is due to its free services and the concentration of several super-specialized units.

This referral hospital's Accident & Emergency Department includes a holding area, an operating theatre, and a resuscitation unit. Twenty-eight (28) patients, on average, undergo emergency non-trauma laparotomy monthly in the operating theatre of this unit, with approximately one (1) out of every five (5) of them receiving blood transfusion (unpublished data, Egbe FE, 2022). Postoperative management of these patients is done in the general surgery wards (endocrine, hepatobiliary, and colorectal surgery wards).

Study Population and Data Collection

The study was approved by the Makerere University School of Medicine Research Ethics Committee (Mak-SOMREC-2022-494 of 09-02-2023) and the Mulago National Referral Hospital Ethics Committee (MHREC 2432 of 17-02-2030). Before inclusion in the study, written consent was obtained from each participant.

Participants in this study included all consecutively recruited adult patients (≥18 years) admitted to the general surgery wards of Mulago National Referral Hospital following emergency non-trauma laparotomy and gave their written consent to be included in the study. They were recruited into either a transfusion-exposed or a non-exposed group. The transfusion-exposed group included participants who were transfused with whole blood or packed cells within 48 hours before surgery (preoperative period), during surgery (intraoperative period), or within 48 hours after surgery (postoperative period). The non-exposed group included participants who had not been transfused any of the above blood products within the abovementioned period. However, all participants transfused within 30 days before the preoperative period were excluded from the study. The rationale for the choice of 48 hours is that from observation, most patients routinely undergo emergency laparotomy within 48 hours of presentation and those requiring transfusion receive such within 48 hours after surgery.

Independent variables, including age, measured in completed years, sex and history of smoking, comorbidities, including presence or absence of diabetes mellitus, immunodeficiency/HIV seropositive, and malignancy, were obtained by interviewing the participants and/or reviewing any formal test results or current drug treatment. Participants’ body mass indices (BMI) were obtained after measuring their weights with a weighing scale and heights with measuring tape. It was recoded as the presence (BMI≥30 kg/m²) or absence (BMI<30 kg/m²) of obesity and the presence (BMI<18.5 kg/m²) or absence (BMI≥18.5 kg/m²) of underweight. The presence or absence of perioperative blood transfusion was obtained from participants’ records. Preoperative haemoglobin and leucocyte count were obtained from participants’ preoperative complete blood count (CBC) results. They were recoded as preoperative anaemia - Hb<10 g/dl - vs. no preoperative anaemia - Hb≥10 g/dl; and preoperative leucocytosis/leucopaenia - WBC>11x10⁹/l or <4x10⁹/l (which is a surrogate marker of preoperative sepsis) vs. no preoperative leucocytosis/leucopenia - 4≤WBC≤11 respectively. Intraoperative findings were obtained from participants’ postoperative notes and included the following: American Society of Anesthesiologists (ASA) score (recoded as high - III/IV/V vs. low - I/II); degree of peritoneal contamination or exudate (classified as clear vs. cloudy/purulent/feculent); cadre of the primary surgeon (a resident/trainee vs. a registrar/specialist); diagnosis (classified as gut perforation vs. bowel obstruction); and duration of surgery (recoded as shorter if ≤120 minutes vs. prolonged if >120 minutes). The latter cut-off for duration of surgery is based on a recent study by Kaushal-Deep et al (2019) in India that reported acceptable limits of mortality rate (≈5%) in paediatric emergency surgery in resource-limited setting if the duration of surgery does not exceed 123.5 minutes (10). Gut perforation included gastroduodenal, ileal, appendicular, gall bladder, and colonic perforations; bowel obstruction included obstructed/strangulated internal/abdominal wall hernia, postoperative adhesion, intussusception, volvulus, and colorectal tumour. The type of surgical procedure was recoded as either procedures with high risk for bowel leak (if there was intraperitoneal bowel repair or a possible bowel perforation was not identified/repaired and included gut perforation repair, resection/anastomosis, abscess drainage, bile drainage) or procedures with low risk for bowel leak (if there was little/no peritoneal exposure to bowel content and included resection/stoma, release of adhesions, hernia reduction/repair, volvulus de-rotation, intussusception reduction).

Participants in both groups were followed up and reviewed clinically on postoperative days 3, 7, 14, 21, and 30 for the onset of an outcome, including surgical site infection and/or mortality. Participants discharged from the hospital before postoperative day 30 and unable to return to the hospital were followed up using telephone interviews.

Figure 1. Flowchart showing participants’ recruitment into the study (See Figure File 1).

Based on the inclusion criteria, 160 adult participants were recruited into the study; no patient was excluded. All participants were included in the final analysis.

Sample Size Estimation and Statistical Analysis

The Fleiss formula for independent cohort studies estimated the sample size assuming a 5% level of significance and an 80% power. Considering the retrospective cohort study conducted on patients receiving transfusion in major emergency laparotomy by Schack et al. (3), 60.1% of the transfused patients experienced a severe surgical complication compared with 28.1% of the non-transfused patients (p<0.001). In addition, in a recent pilot study based on records in our local hospital setting, 17% of patients undergoing emergency non-trauma laparotomy were transfused, and 83% were not. This implies the ratio of unexposed to transfusion-exposed patients, m = 83/17 = 4.89 (unpublished data, Egbe FE, 2022). A sample size of 160 participants (exposed = 28; non-exposed = 132) was therefore obtained following a 10% adjustment for loss to follow-up.

All statistical analyses were performed using CDC EPI INFO version 7.2.5.0, IBM SPSS version 29.0.1.0, and Stata Corp LP Stata/MP version 14.0. Categorical data are presented as absolute numbers and percentages, n (%), and continuous variables with skewed distribution are expressed as the medians ± interquartile range. Bivariate analyses involving categorical independent variables and dependent variables were performed using two-sided Fischer's exact tests, while analyses involving categorical independent variables and continuous dependent variables were performed using the Mann-Whitney U test. Two-sided p<0.05 was accepted as statistically significant. Data distribution is presented using frequency tables.

To assess the association between perioperative blood transfusion and 30-day risk of surgical site infection, bivariate logistic regression analysis was used to determine the association between independent variables and 30-day surgical site infection. The associations were presented as relative risks (RRs) with 95% confidence intervals (CIs) and p values. All independent variables with p<0.2 were considered for the multivariate logistic regression model. A test for multicollinearity was performed using variance inflation factor analysis, and cloudy/purulent/feculent exudate, which was collinear with gut perforation diagnosis, was dropped from the model. Multivariate logistic regression analysis assessed the association between perioperative transfusion and the 30-day risk of surgical site infection adjusted for confounders. The associations were reported as relative risks (RRs) with 95% confidence intervals (CIs) and p values. Statistical significance was defined by a two-sided p<0.05.

To assess the association between perioperative blood transfusion and 30-day mortality risk, bivariate Cox regression analysis was used to determine the association between independent variables and 30-day mortality. The associations were presented as hazard ratios (HRs) with 95% confidence intervals (CIs) and p values. All independent variables with p<0.2 were considered for the multivariate Cox regression model. A test for multicollinearity was performed using variance inflation factor analysis, and cloudy/purulent/feculent exudate, which was collinear with bowel obstruction diagnosis, was dropped from the model. Multivariate Cox regression analysis assessed the association between perioperative transfusion and 30-day mortality adjusted for confounders. The associations were reported as hazard ratios (HRs) with 95% confidence intervals (CIs) and p values. Statistical significance was defined by a two-sided p<0.05.

Over the study period, 160 adult participants undergoing emergency non-trauma laparotomy were recruited: 28 (17.5%) were transfusion-exposed, and 132 (82.5%) were non-exposed. They completed the 30-day follow-up evaluation and were included in the final analysis (Figure 1). Of those transfused, 28.6% (n=8) of the participants were transfused for the first time within 48 hours before surgery; 53.6% (n=15) were transfused during surgery, while 17.8% (n=5) received their transfusion within 48 hours after surgery. Table 1 shows that preoperative haemoglobin (10.5 vs. 14.2, p<0.0001), preoperative leucocyte count (6.5 vs. 9.2, p=0.029), and quantity of blood transfused (2 vs. 0, p<0.0001) were significantly different in the transfusion-exposed compared to the non-exposed groups (Table 1).

Table 1. Characteristics of the study population stratified by transfusion

Variable

Transfusion-exposed, n = 28 (17.5%)

Non-exposed,

n = 132 (82.5%)

p-value

Sex

Female

Male

13 (27.7)

15 (13.3)

34 (72.3)

98 (86.7)

0.039 **

Age (years), Mdn (Q1, Q3)

36.0 (21.0, 48.0)

37 (24.0, 51.0)

0.639

Preoperative Haemoglobin(g/dl), Mdn (Q1, Q3)

10.5 (7.7, 13.3)

14.2 (12.4, 16.0)

<0.001 **

Quantity of blood transfused (units), Mdn (Q1, Q3)

2 (1, 3)

0 (0, 0)

<0.001 **

Cadre of Primary surgeon

Registrar

Resident

6 (40.0)

22 (15.2)

9 (60.0)

123 (84.8)

0.027 **

Preoperative leucocyte (x 10⁹/l),

Mdn (Q1, Q3)

6.5 (4.4, 9.6)

9.2 (6.3, 12.5)

0.029 **

ASA score

High (III, IV, V)

Low (I, II)

14 (26.4)

14 (13.1)

39 (73.6)

93 (86.9)

0.047 **

Immunodeficiency

Yes

No

5 (35.7)

23 (15.8)

9 (64.3)

123 (84.2)

0.073

Malignancy

Yes

No

5 (27.8)

23 (16.2)

13 (72.2)

119 (83.8)

0.319

Surgery duration (minutes),

Mdn (Q1, Q3)

102.5 (85.0, 177.5)

110 (76.5, 150.0)

0.449

Type of surgical procedure

High risk for bowel leak

Low risk for bowel leak

18 (16.2)

10 (20.4)

93 (83.8)

39 (79.6)

0.508

Diabetes mellitus

Yes

No

0 (0.0)

28 (18.1)

5 (100.0)

127 (81.9)

0.588

BMI (kg/m²), Mdn (Q1, Q3)

20.2 (18.0, 22.6)

20.6 (18.8, 22.3)

0.689

Peritoneal exudate

Cloudy/purulent/feculent

Clear

16 (18.2)

12 (16.7)

72 (81.8)

60 (83.3)

0.837

Smoking

Yes

No

3 (16.7)

25 (17.6)

15 (83.3)

117 (82.4)

1.000

Diagnosis

Bowel obstruction

Gut perforation

13 (17.6)

15 (17.4)

61 (82.4)

71 (82.6)

1.000

ASA = American Society of Anesthesiologists; BMI = Body Mass Index

** Statistically significant (p<0.05)

Association between Perioperative Blood Transfusion and 30-day Risk of Surgical Site Infection.

In this study, the overall incidence of surgical site infection was 34.4%. Supplementary Table s1 shows a bivariate analysis of the factors associated with 30-day surgical site infection. Based on the p<0.2 significance level, perioperative blood transfusion (71.4% vs. 26.5%, p<0.0001), preoperative leucocytosis/leucopenia (44.6 vs. 27.4%, p=0.028), preoperative anaemia (61.5 vs. 32.0%, p=0.063), cloudy/purulent/feculent exudate (40.9 vs. 26.4%, p=0.066), young-to-middle-age adults (37.6 vs. 18.5%, p=0.049), gut perforation diagnosis (40.7 vs. 27.0%, p=0.095), female sex (44.7 vs. 30.1%, p=0.099) and registrar-led surgical team (53.3 vs. 32.4%, p=0.151) were considered for multivariate analysis (Supplementary Table s1).

Supplementary Table s1. Thirty-day risk of surgical site infection based on bivariate analysis.

Following variance inflation factor analysis for multicollinearity, cloudy/purulent/feculent exudate, collinear with gut perforation diagnosis, was dropped from the multivariate regression model. Multivariate logistic regression analysis (method: forced entry) of the association of perioperative blood transfusion and 30-day risk of surgical site infection adjusted for confounders identified transfusion exposure and preoperative leucocytosis/leucopenia as independent risk factors for 30-day surgical site infection among participants undergoing emergency non-trauma laparotomy at Mulago National Referral Hospital, Kampala, Uganda. Perioperative blood transfusion results in a 7.81 times higher risk of surgical site infection within 30 days of emergency non-trauma laparotomy than no perioperative transfusion (RR, 7.81; 95% CI, 2.58 – 23.63; p=0.0003). In addition, preoperative leucocytosis/leucopenia resulted in 2.19 times higher risk of surgical site infection within 30 days of emergency non-trauma laparotomy than a normal preoperative leucocyte count (RR, 2.19; 95% CI, 1.04 – 4.65; p=0.040) (Table 2).

Table 2. Thirsty-day risk of surgical site infection based on multivariate logistic regression analysis

Variable

Relative risk (95% CI)

p-value

Perioperative blood transfusion

No

Yes

1

7.81 (2.58 – 23.63)

< 0.001 **

Preoperative leucocytosis/leucopenia

No

Yes

1

2.19 (1.04 – 4.65)

0.040 **

Sex

Male

Female

1

1.98 (0.86 – 4.55)

0.107

Diagnosis

Bowel obstruction

Gut perforation

1

1.93 (0.86 – 4.34)

0.113

Age

Elderly adults (≥ 60 years)

Young-to-middle age adults (18 – 59 years)

1

2.39 (0.73 – 7.83)

0.151

Cadre of primary surgeon

Resident

Registrar

1

1.89 (0.53 – 6.74)

0.329

Preoperative anaemia

No

Yes

1

0.58 (0.12 – 2.72)

0.489

CI = Confidence Interval; ** Statistically significant (p<0.05)

Association between Perioperative Blood Transfusion and 30-day Mortality Risk

In this study, the overall incidence of mortality was 9.4%. Supplementary Table s2 shows a bivariate Cox regression analysis of the factor associated with 30-day mortality. Based on the p<0.2 significance level, perioperative blood transfusion (25.0% vs. 6.1%, p=0.003), elderly age group (28.6 vs. 5.3, p<0.001), high ASA score (18.9 vs. 4.7, p=0.009), immunodeficiency (28.6 vs. 7.5, p=0.013), cloudy/purulent/feculent exudate (5.7 vs. 13.9 p=0.087), bowel obstruction (13.5 vs. 5.8, p=0.106) and procedures with high risk for bowel leak (7.2 vs. 14.3, p=0.169) were considered for multivariate analysis (Supplementary Table s2).

Supplementary Table s2. Thirty-day risk of mortality based on bivariate Cox regression analysis.

Following variance inflation factor analysis for multicollinearity, cloudy/purulent/feculent exudate, collinear with bowel obstruction, was dropped from the multivariate Cox regression model. Multivariate Cox regression analysis (method: forced entry) of the association of perioperative blood transfusion and 30-day mortality risk identified transfusion exposure and old age as independent risk factors for 30-day mortality among participants undergoing emergency non-trauma laparotomy at Mulago National Referral Hospital, Kampala, Uganda. Perioperative blood transfusion had a 3.36 times higher mortality risk within 30 days of emergency non-trauma laparotomy than no perioperative blood transfusion (HR, 3.36; 95% CI, 1.11 – 10.25; p=0.033). Furthermore, adults aged 60 years and above had a 5.50 times higher risk of mortality than adults aged less than 60 years (HR, 5.50; 95% CI, 1.67 – 18.11; p=0.005) (Table 3).

Table 3. Thirty-day risk of mortality based on multivariate Cox regression analysis

Variable

Hazard Ratio (95% CI)

p-value

Perioperative blood transfusion

No

Yes

1

3.36 (1.11 – 10.25)

0.033 **

Age

Young-to-middle-age adults (18 – 59 years) Elderly adults (≥ 60 years)

1

5.50 (1.67 – 18.11)

0.005 **

Immunodeficiency

No

Yes

1

3.00 (0.82 – 10.93)

0.097

ASA score

Low (I, II)

High (III, IV, V)

1

1.86 (0.56 – 6.16)

0.310

Type of Surgical Procedure

Low risk for bowel leak

High risk for bowel leak

1

0.75 (0.22 – 2.59)

0.648

Diagnosis

Gut perforation

Bowel obstruction

1

1.01 (0.27 – 3.85)

0.986

ASA = American Society of Anesthesiologists; CI = Confidence Interval; ** Statistically significant (p<0.05)

This prospective cohort study found that patients receiving perioperative blood transfusions had 7.81 times more risk of surgical site infection than those not transfused (p<0.001); patients with preoperative leucocytosis/leucopenia had 2.19 times more risk of surgical site infection than those with normal preoperative leucocyte count (p=0.040). In addition, the study found that patients receiving perioperative blood transfusion had 3.36 times more risk of dying within 30 days of emergency non-trauma laparotomy than those who were not transfused (p=0.033); adults aged 60 years and above had 5.50 times more risk of dying within 30 days of emergency non-trauma laparotomy than adults aged less than 60 years (p=0.005).

Patients receiving perioperative transfusion were more likely to have surgical site infection than those not receiving transfusion. This is consistent with several recently published data from high-income countries suggesting that perioperative transfusion is an independent risk factor for surgical site infection. A retrospective cohort study by Schack et al. (2021) involving patients undergoing major emergency laparotomy (3), Jiang et al. (2022) concerning colorectal cancer complications (4), McSorley et al. (2020) involving patients undergoing colorectal cancer surgery (5), all reveal an association between blood transfusion and increased risk of postoperative complication defined by a Clavien-Dindo score of at least 3a which includes surgical site infection. Other studies found a similar association between blood transfusion and postoperative infection in patients undergoing surgery for Crohn’s disease (6), gastrectomy for gastric cancer (11), and pancreaticoduodenectomy (12). With these findings, we suggest, as a means of reducing the rate of surgical site infection, the establishment of pre-emptive daily monitoring of surgical wounds, which should be left open in case of preoperative or intraoperative transfusion, expeditious management upon identification of wound infection, and delayed wound closure. The current study also found that preoperative leucocytosis/leucopenia was associated with surgical site infection. In another study involving non-neonatal paediatric surgery patients, concurrent infection was associated with an increased risk of surgical site infection (13). The covariates, preoperative leucocytosis/leucopenia and concurrent infection, may be surrogate markers for preoperative sepsis, which will predispose patients to postsurgical wound infection by the haematogenous bacterial spread.

Participants receiving perioperative transfusion were more likely to die within 30 days of emergency non-trauma laparotomy compared to those who were not transfused in the current study. These findings were consistent with recently published data that reported perioperative transfusion as an independent risk factor for mortality, such as the study by Schack et al. (2022) involving patients undergoing major emergency laparotomy (3), Jiang et al. (2022) concerning colorectal cancer complications (4) and McSorley et al. (2020) involving patients undergoing colorectal cancer surgery (5). In addition, Xue et al. (2016) asserted that perioperative transfusion was associated with poor survival in patients with POHb >100 g/L (p<0.001), unlike in transfused patients with POHb between 70 and 100 g/L (p = 0.191) (11). Previous studies have shown that restrictive transfusion triggers of <8 g/dl avoid blood transfusion in 25% of patients without increasing the risk of morbidity compared to the liberal strategy (14). This restrictive strategy is also not inferior to the liberal approach in terms of preventing mortality in critically ill patients (15) (16). These findings illustrate the need to balance the benefits and risks of blood transfusion in patients undergoing laparotomy and instituting restrictive over liberal guidelines for transfusion. The current study also found that participants aged ≥60 years were more likely to die within 30 days of emergency non-trauma laparotomy than those aged <60 years. This is probably due to stress-induced immunosuppression following major surgery that worsens the already frail elderly, resulting in worse outcomes compared to younger persons.

Transfusion-related immunomodulation (TRIM) was first described over three decades ago in renal transplant recipients who demonstrated improved allograft survival after allogeneic blood transfusion. It was postulated that exposure to allogeneic blood transfusions induces clinically significant immunosuppression and allo-sensitization in recipients (17) (18). This eventually leads to postoperative bacterial infection and cancer recurrence while improving outcomes in renal allograft transplantation (19). In addition, previous studies assert that major emergency surgery, including laparotomy, contributes to immunomodulation by suppressing TH cell function during the early postoperative period and reducing the secretion of IL-2, INF-γ, TNF-α (stimulate TH1), and IL-4 (stimulate TH2) hence increasing host susceptibility to septic complications (20). Furthermore, perioperative allogeneic blood transfusion worsens stress-induced postsurgical immunosuppression by impairing NK cell activity (21).

There were several limitations to our study. First, there was no transfusion protocol indicating a transfusion trigger or threshold. Consequently, some patients with anaemia were not transfused, while others without anaemia were transfused. In addition, this study was performed with a small sample size; hence, the large number of covariates assessed affected the reliability of our results, as shown by the wide confidence intervals for the measure of association. Moreover, neither randomization nor matching was performed to reduce bias; hence, our results must be interpreted with these in mind. Lastly, patient-related variables were identified by prior diagnosis and as declared by the patient. This means there was reporting bias as no further diagnostic test was performed in the study.

Among patients undergoing emergency non-trauma laparotomy in this large urban tertiary hospital in a low-income setting, perioperative blood transfusion resulted in a 7.81 times higher risk of surgical site infection and a 3.36 times higher risk of mortality than no perioperative transfusion. Although the current study provides crucial contextual evidence, more substantial evidence would be generated using a multicentre study with a larger sample size. Nevertheless, our findings provide some support for the restrictive use of blood transfusion among patients undergoing emergency non-trauma laparotomy in low-income settings.

ASA: American Society of Anesthesiologists

BMI: body mass index

CBC: complete blood count

CDC: Centers for Disease Control

CI: confidence interval

HIV/AIDS: Human immunodeficiency virus/acquired immune deficiency syndrome

HR: hazard ratio

IL-2: interleukin-2,

INF-γ: interferon-γ

Mak-SOMREC: Makerere University School of Medicine Research Ethics Committee

MNRH: Mulago National Referral Hospital

MHREC: Mulago Hospital Research Ethics Committee

NK: Natural Killer

OR: odds ratio

POHb/Hb: Preoperative Haemoglobin/Haemoglobin

RR: relative risk

SPSS: Statistical Package for the Social Sciences

SSI: surgical site infection

TH: Helper T cell

TNF-α: Tumour Necrosis Factor-α

TRIM: transfusion-related immunomodulation

VIF: variance inflation factor

WBC: white blood cell

Ethical Approval and Consent to Participate

We obtained ethical approval No. Mak-SOMREC-2022-494 of 09-02-2023 from the Makerere University School of Medicine Research Ethics Committee (Mak-SOMREC) and administrative approval No. MHREC 2432 of 17-02-2023 from the Mulago National Referral Hospital Research Ethics Committee to conduct this study. Before inclusion in the study, we explained to potential participants what the study was about, the benefits and risks; informed them of any special incentive or remuneration for participation; assured them of confidentiality, told them of the right to opt out of the study if needed; and obtained their individual written consent.

Consent for Publication

Not applicable

Availability of Data and Materials

The dataset supporting the conclusions of this article is included within the article and its additional files.

Competing Interests

The authors declare that they have no competing financial or non-financial interests.

Funding

None

Authors’ Contributions

FEE, PO, RM and MO conceptualized and designed the study. FEE collected the data and drafted the manuscript. FEE, PO and RNI analysed and interpreted the data. All authors critically reviewed and approved the final version of the manuscript.

Acknowledgments

We thank Sahidu T. Ebot and Frank L. Tianyi Tianyi for directing our data analysis; the administration of Mulago National Referral Hospital for permitting us to conduct this study in the institution; and the participants and their attendants for giving their consent to participate in this study and for consistently providing the information needed for its completion.

Authors’ Information

F.E.E, B.M.L.S, M.D

Resident, Department of Surgery, School of Medicine, College of Health Sciences, Makerere University, Kampala, Uganda.

E-mail: [email protected]om, [email protected]

RM, MBChB, M. Med (Surgery)

Lecturer & PhD fellow, Department of Surgery, School of Medicine, College of Health Sciences, Makerere University, Kampala, Uganda.

E-mail: [email protected], [email protected]

MO, MBChB, M. Med (Surgery), F. Hepatobiliary & Liver Transplant Surgery, F. Min Access Surgery

Senior Lecturer, Department of Anatomy, School of Biomedical Sciences, College of Health Sciences, Makerere University, Kampala, Uganda.

Hepatobiliary Surgeon, Lubaga Hospital, Kampala, Uganda.

E-mail: [email protected], [email protected]

R.N.I, MBChB, M. Med (Surgery)

General Surgeon, Moyo General Hospital, Moyo, Uganda

E-mail: [email protected]

PO, MBChB, M. Med (Surgery), PGDip MedEd, FCS-ECSA

Lecturer, Department of Surgery, School of Medicine, College of Health Sciences, Makerere University, Kampala, Uganda.

Research Scholar, Royal College of Surgeons of Ireland, University of Medicine & Health Sciences, Ireland.

E-mail: [email protected], [email protected]

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The authors declare no competing interests.

SupplementaryTables1Thirtydayriskofsurgicalsiteinfectionbasedonbivariateanalysis.docx
Supplementary Table s1. Thirty-day risk of surgical site infection based on bivariate analysis.
SupplementaryTables2ThirtydayriskofmortalitybasedonbivariateCoxregressionanalysis.docx
Supplementary Table s2. Thirty-day risk of mortality based on bivariate Cox regression analysis.
AdditionalFile1VisualAbstract.pptx
Visual Abstract
AdditionalFile2TRANSFUSIONSSIMORTALITYMULAGOUGANDA.xls
Data Set

Effect of perioperative blood transfusion on complications following emergency non-trauma laparotomy in Mulago hospital: A prospective cohort study.

Status:

Version 2

Abstract

Figures

Background

Methods

Study Design and Setting

Study Population and Data Collection

Sample Size Estimation and Statistical Analysis

Results

Association between Perioperative Blood Transfusion and 30-day Risk of Surgical Site Infection.

Association between Perioperative Blood Transfusion and 30-day Mortality Risk

Discussion

Conclusion

Abbreviations

Declarations

Ethical Approval and Consent to Participate

Consent for Publication

Availability of Data and Materials

Competing Interests

Funding

Authors’ Contributions

Acknowledgments

Authors’ Information

References

Additional Declarations

Supplementary Files

Status:

Version 2