Blood transfusion in pediatric intracranial tumor surgery

doi:10.21203/rs.3.rs-4812647/v1

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Blood transfusion in pediatric intracranial tumor surgery

https://doi.org/10.21203/rs.3.rs-4812647/v1

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Background

Pediatric central nervous system tumors are the most common solid tumors in children and leading cause of cancer-related morbidity and mortality. Various factors may influence the practice of blood transfusion during this tumor diagnosis. The primary aim of this study was to determine the factors that may influence intraoperative blood transfusion in pediatric patients undergoing surgery for intracranial tumors and to predict patients who may require blood transfusion

Methods

A retrospective study was performed in all pediatric patients younger than 15 years who underwent craniotomy for brain tumor removal from January 2018 to December 2023 in our institution. Preoperative, intraoperative and postoperative data were collected from medical and store anesthesia records. The predictors of intraoperative blood transfusion were determined using multivariate logistic regression.

Results

A total of 138 patients were included. Intraoperative blood transfusion was performed in 62 (44.9%) patients. In multivariate regression analysis age < 4 years and operating time > 490 minutes were determined as independent variables in terms of need for intraoperative blood transfusion. It was determined that the need for transfusion was higher in patient who were operated on urgently and patients with comorbidities (p = 0.023, p = 0.005).

Conclusion

In conclusion, the findings obtained in this study suggest that age and surgical duration are independent risk factors for intraoperative blood transfusion in pediatric patients undergoing surgery for intracranial tumors. Particularly, in younger patients and prolonged surgeries, closer monitoring and awareness may enhance early detection, leading to the prevention of complications.

pediatric neuroanesthesia

volatil anesthesia

blood transfusion

Pediatric central nervous system (CNS) tumors are the second most common malignancies in childhood and the most frequent solid tumors in children. In the United States, the incidence of primary brain and other CNS tumors in children and adolescents is approximately 5.67 per 100,000 individuals per year.[1] Supratentorial tumors are more commonly observed in infants and children up to 3 years of age and after the age of 10 years, whereas infratentorial tumors are more common between the ages of 4 and 10 years.[2] In younger children, embryonal tumors such as medulloblastoma or atypical teratoid/rhabdoid tumor have a higher incidence, whereas in older individuals, tumors of glial origin are more frequently encountered. The symptoms and signs that may be observed in patients depend on various factors such as the location of the tumor, the age of the child, and the growth rate of the tumor.[2]

Anemia is one of the most common medical complications that occur during surgical procedures.[3] In general, studies encompassing all brain surgery procedures have reported an allogenic transfusion rate ranging from 1.7–5.4%.[4–5] However, the reported transfusion incidence for specific patient populations undergoing intracranial neurosurgery ranges from 10–95%. The risks associated with allogenic blood transfusion are significant, and these risks have been particularly well-documented in children.[6] Transfusion-related complications include infectious diseases, allergic reactions, transfusion-related lung injury, and hemolytic reactions.[7] Allogenic blood transfusion may increase morbidity and mortality in the surgical population.[8]

Prospective studies have demonstrated that restrictive transfusion strategies are as effective as liberal strategies and, in some cases, may even be superior.[9–12] However, in recent years, restrictive transfusion strategies have gained prominence worldwide because of clinical studies demonstrating significant transfusion-related risks and also the escalating costs associated with transfusion.

The primary aim of this study was to determine the factors that may influence intraoperative blood transfusion in pediatric patients undergoing surgery for intracranial masses and to predict patients who may require blood transfusion.

All pediatric patients with brain tumor operated at Dicle University Hospital between January 2018 and December 2023 were included in this retrospective and cross-sectional study. Ethical approval was received from the ethics committee of Dicle University Faculty of Medicine. Between the specified dates, patients undergoing surgery for pediatric brain tumors were assessed based on the American Society of Anesthesiologists (ASA) classification, perioperative hemodynamic data, the need for intraoperative blood transfusion, intraoperative use of inotropes, type of anesthesia administered, anesthetic agents used, postoperative status of patients (intubated or extubated), duration of stay in the intensive care unit (ICU), whether a central venous catheter (CVC) was inserted, and the presence of CVC complications or malrotation. Radiological images and pathology records were reviewed. Patients aged ≥ 15 years and those undergoing brain surgery for reasons other than brain tumors were not included in the study.

All surgical procedures were performed under general anesthesia. The choice between inhalation and intravenous anesthesia induction technique was made by the attending anesthesiologist based on the presence of signs of intracranial hypertension in the patient. Following endotracheal intubation, general anesthesia was maintained with intravenous infusion of remifentanil (0.02–0.2 µg/kg/min) and propofol (Propofol, Fresenius Kabi, Sweden) (6–12 mg/kg/h) or sevoflurane (Sevoflurane Liquid 100%, Queenborough) at a concentration < 1 MAC. Routine intraoperative monitoring included electrocardiography, noninvasive arterial blood pressure, capnography, pulse oximetry, body temperature, and urinary output through a catheter. Following the induction of general anesthesia, an arterial catheter and a central venous line were placed.

Demographic data including age, sex, and body weight, along with ASA classification, preoperative hemoglobin levels, coagulation parameters, and localization of the intracranial mass (supratentorial or infratentorial based on tumor histology) were recorded. Intraoperative data including duration and year of operation, intraoperative position, intraoperative inotrope use, blood transfusion, and placement of CVC and arterial catheter were recorded. All patients were transferred to the ICU for postoperative follow-up. In the postoperative period, whether the patients were intubated or extubated, postoperative hemoglobin and hematocrit values, duration of ICU stay, and length of hospitalization were recorded.

3. Statistical Analysis

SPSS 16.0 software for Windows (SPSS Inc., Chicago, IL, USA) was used for the statistical analysis. Continuous data are expressed as mean and standard deviation, and categorical data are expressed as frequency and percentage. The categorical data of the groups were compared using the Chi-square and Fisher’s exact tests. The Kolmogorov-Smirnov test was used to determine whether the numerical data were normally distributed. The Student's t-test was used to analyze data with a normal distribution, while the Mann–Whitney U test was used to analyze no normally distributed data. In all comparisons, p < 0.05 was considered significant.

A total of 140 patients were included in the study. The records of one patient could not be obtained, and one patient was excluded from the study because of postoperative transfer, and the study was completed with 138 patients. Patients were divided into two groups according to the need for blood transfusion: Group 1 and Group 2. Group 1 consisted of 62 (44.9%) patients who received transfusion. Group 2 consisted of 76 (55.1%) patients who did not need transfusion (Fig. 1).

Univariate analysis

The groups were compared in terms of demographic data, preoperative laboratory values, intraoperative hemodynamic data, and other characteristics. Demographic data showed that mean age and body weight were lower in Group 1 than Group 2 (p = 0.006 for both data), and the incidence of comorbidities was higher in Group 1 (p = 0.005). There was no statistically significant difference between the two groups in terms of sex and ASA classification (Table 1).

Table 1

Demographic Data of Patients
Parameters	Group 1 (RBC-Transfusion, n:62 )		Group 2 (Non-RBC Transfusion n:76)		p value
	Mean	SD	Mean	SD
Age (y)	5.82	4.57	7.89	4.89	0.006
Weight	22.69	15.03	29.33	15.43	0.006
Hemoglobin (g/L)	11.56	1.32	12.36	1.63	0.027
Hematocrit (%)	35.94	3.9	37.34	4.31	0.15
Intensive care hospitalization period	22.21	17.13	18.33	14.38	0.3
Anesthesia duration	578.52	235.66	452.95	200.58	0.001
Surgery duration	545.82	227.78	421.15	191.36	0.001
Preoperative SpO²	97.95	1.5	98.12	2.11	0.1
Intraoperative SpO²	99.18	1.39	99.09	1.03	0.85
Postoperative SpO²	98.62	2.04	98.51	1.31	0.93
Preoperative heart rate (bpm/min)	113.08	20.7	107.45	18.72	0.09
Intraoperative heart rate (bpm/min)	107.05	19.04	100.84	19.66	0.07
Postoperative heart rate (bpm/min)	116.39	26.45	96.47	19.06	< 0.001
Preoperative MAP (mmHg)	72.48	11.12	75.37	11.23	0.13
Intraoperative MAP (mmHg)	67	8.81	72.71	10.51	< 0.001
Postoperative MAP (mmHg)	65.19	9.28	71.48	9.81	0.001
	Frequency	Percent	Frequency	Percent
Gender					0.15
Male	37	26.8	36	26.1
Female	25	18.1	40	29
ASA classification					0.054
1	8	5.8	19	13.9
2	34	24.8	38	27.7
3	15	10	19	13.9
4	4	2.9	0	0
Surgery type					0.023
Emergency	25	18.1	17	12.3
Elective	37	26.8	59	42.8
Comorbitidy					0.005
Yes	13	9.4	4	2.9
No	49	35.5	72	52.2
Anesthetic agent					0.25
Sevoflurane	21	15.2	19	13.8
TIVA	41	29.7	57	41.3
Inotrop using					0.025
Yes	4	2.9	0	0
No	58	42.1	76	100
Postoperative					0.004
Extubated	10	7.2	29	21
Intubated	52	37.7	47	34.1
Mortality					0.053
Nonsurvivor	8	5.8	3	2.2
Survivor	54	39.1	73	52.9
Patient positions					0.48
Supine	28	20.3	39	28.3
Prone	30	21.7	28	20.3
Sitting	2	1.4	5	3.6
Lateral	2	1.4	4	2.9
Central venous catheter					0.17
No catheter	10	7.2	21	15.2
Right jugular vein	45	32.6	45	32.6
Left jugular vein	3	2.2	4	2.9
Right infraclavıcular vein	1	0.7	5	3.6
Femoral vein	3	2.2	1	0.7
Central venous catheter malposition					0.22
Yes	7	5.1	4	2.9
No	54	39.1	72	52.2
SPO2:Oxygen saturation, MAP; Mean arterial pressure, ASA:American Society of Anesthesiologist

Comparison of the groups in terms of emergency and elective surgical procedures showed that the need for transfusion was significantly higher in patients undergoing emergency surgery than patients undergoing elective surgery (p = 0.023). Transfusion was not required for 42.8% (59 patients) of patients undergoing elective surgery. Comparison of groups in terms of preoperative laboratory values showed that preoperative hemoglobin levels were significantly lower in Group 1 than Group 2 (p = 0.027). The duration of anesthesia and surgery was longer in Group 1 than Group 2 (p = 0.001). Analysis of the groups in terms of inotrope use showed that all patients requiring intraoperative inotropes were in Group 1 (p = 0.025). Analysis of the patients in terms of postoperative ICU discharge status showed that most of the intubated patients (52 patients, 37.7%) were in Group 1 (p = 0.004) (Table 1).

Comparison of groups in terms of intraoperative heart rate and mean arterial pressure (MAP) showed that patients in Group 1 had higher postoperative heart rates (p < 0.001) and lower intraoperative and postoperative MAP values (p < 0.001 and p = 0.001, respectively) than Group 2 (Table 1).

Multivariate analysis

Multivariate analysis showed that age ≤ 4 years and surgery duration > 490 min were independent risk factors associated with intraoperative blood transfusion requirement (p = 0.027 and p = 0.016, respectively) (Table 2). Having a preoperative hemoglobin value < 13 g/dL was not an independent risk factor for blood transfusion (p = 0.148). The receiver operating characteristic curve analysis for predicting intraoperative blood transfusion need using this model yielded an area under the curve of 0.768 (95% CI = 0.692–0.839) (Fig. 1).

Table 2

Predictive factors for intraoperative blood transfusion for brain tumor removal in multivariate logistic regression
			95% Confidence Interval
Predictor	p-value	Odds ratio	Lower	Upper
Age ≤ 4	0.027	2.927	11.294	7.586
Duration of surgery > 490 min	0.016	3.063	12.268	7.650
Preoperative Hgb < 13	0.148	2.636	0.7094	9.797

The results obtained in the present study, which investigated factors influencing intraoperative blood transfusion in pediatric patients undergoing surgery for intracranial masses, showed that 44.9% of patients needed intraoperative blood transfusion. Patient age ≤ 4 years and operation duration > 490 min were identified as independent risk factors for intraoperative blood transfusion in this surgical population.

In the relevant literature, Vassal et al. conducted a retrospective study spanning 3 years, assessing the outcomes of 110 pediatric patients undergoing brain tumor resection. The authors emphasized that patient age < 4 years, operation duration > 270 min, and preoperative hemoglobin concentration < 12.2 g/dL were key factors associated with allogenic blood transfusion.[13] In a retrospective study evaluating 297 pediatric brain tumor cases, Zhang et al. reported that age, preoperative hemoglobin level, duration of anesthesia, tumor size, unclear tumor margin, intraoperative vasopressor infusion, and tumor grade were independent predictors for RBC transfusion.[14] Hsu et al. evaluated 99 adult patients operated for intracranial meningioma and reported that larger tumor size and prolonged operation time increased the risk of severe bleeding.[15] Rajagopalan et al. conducted a retrospective study in 2019, where they categorized and examined 456 adult patients who underwent intracranial tumor surgery into four groups based on the amount of bleeding. According to the results, female sex, hypertension, tumor size > 5 cm, and operation time > 300 min were identified as risk factors for bleeding.[16] The results obtained in the present study regarding the parameters evaluated are consistent with the literature. However, although preoperative hemoglobin levels were significantly lower in the patient groups receiving transfusion, contrary to the literature, preoperative hemoglobin was not identified as an independent risk factor for blood transfusion in the present study. This may be because of the high cutoff value set for hemoglobin level (< 13 g/dL).

While the safety of blood product administration has significantly improved in recent years, risks associated with blood transfusion persist. These risks may include allergic reactions, transmission of infectious agents, acute hemolytic reactions, lung injury, and immunomodulation.[6] In a retrospective study conducted in 2011, Laurent et al. examined the relationship between blood transfusion and 30-day morbidity and mortality in 10,100 patients. The authors concluded that intraoperative blood transfusion in surgical patients with severe anemia is associated with high morbidity and mortality.[7] In a retrospective study including a large patient cohort over a 5-year period, Rolston et al. emphasized that complications including bleeding were more common in cranial surgeries and that receiving > 4 units of blood transfusion was significantly associated with postoperative complications.[5] Data related to postoperative mobility were not available in the present study. We did not find a significant relationship between mortality and blood transfusion. This may be because of the fact that subgroup analysis could not be performed based on the amount of transfusion. The necessary data for this analysis were not available in the hospital information system.

Another result was that the need for blood transfusion was higher in emergency cases. This expected result was consistent with the literature. Similar to the present study, Cohen et al. examined 8,924 adults undergoing cranial surgery in their article published in 2017 and reported that patients undergoing emergency surgery required almost twice as much blood transfusion.[17]

Piastra et al., who conducted one of the studies examining the relationship between age and blood transfusion in pediatric cases, examined 43 patients aged ≤ 1 year who underwent brain tumor surgery and were admitted to the pediatric ICU. The authors reported that the mean age was significantly lower in patients with intraoperative blood loss exceeding the preoperative blood volume.[18] Similarly, in the present study, the mean age of the group receiving transfusion was significantly lower than the other group, and patient age ≤ 4 years was identified as an independent risk factor for blood transfusion.

The present study is subject to certain limitations that warrant consideration. The major limitation of this study is the unavailability of intraoperative blood loss and transfused blood volumes in the hospital records. Another limitation of the study is its retrospective and single-center design. There is a need for prospective and multicenter studies on the subject. Finally, given the retrospective design of the present study, the target hemoglobin level for the decision for transfusion was not fully standardized within our population. The decision for transfusion was modulated based on the amount of intraoperative blood loss, hemodynamic status, urinary output, and blood clotting parameters.

In conclusion, the findings obtained in this study suggest that age and surgical duration are independent risk factors for intraoperative blood transfusion in pediatric patients undergoing surgery for intracranial masses. Particularly, in younger patients and prolonged surgeries, closer monitoring and awareness may enhance early detection, leading to the prevention of complications.

CNS

Central Nervous System

ASA

American Society of Anesthesiologists

ICU

Intensive Care Unit

CVC

Central Venous Catheter

MAP

Mean Arterial Pressure

Acknowledgements

We thank Rachel Sandison, MME; Education, Research & Innovation Coordinator for proof-reading this manuscript.

Authors’ contributions

All authors contributed to the study’s conception and design. The first draft of the manuscript was written by HTS,ÖO, OU, and SS, and all authors commented on previous versions of the manuscript. Material preparation: HTS and FÇ. Data collection: FŞ and KA. Analysis was performed by HTS and BA. Review and editing: SS, BG, and RTT. All authors read and approved the final manuscript.

Funding

This research received no external funding.

Availability of data and materials

All data generated or analyzed during this study are included in this article. Further inquiries can be directed to the corresponding author.

Ethics approval and consent to participate

This study was initiated after obtaining approval from the Ethics Committee of Dicle University Faculty of Medicine Non-Interventional Clinical Research dated March 20, 2024 (number 99).

Consent for publication

Written informed consent was obtained from all patients and/or their guardians.

Competing interests

The authors declare that they have no competing interests.

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No competing interests reported.

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You are reading this latest preprint version

Blood transfusion in pediatric intracranial tumor surgery

Status:

Version 1

Abstract

Background

Methods

Results

Conclusion

Figures

Introduction

Material and Methods

3. Statistical Analysis

Results

Discussion

Conclusions

Abbreviations

Declarations

References

Additional Declarations

Status:

Version 1