Effects of modified exchange blood transfusion therapy on infants with severe pertussis: a case-control study
Highlight box
Key findings
• In this case-control study, including 31 infants with severe pertussis, the mortality rate was significantly lower in those who underwent modified exchange blood transfusion (ET) compared with those who received conventional treatment (16.7% vs. 52.6%). Modified ET effectively reduced white blood cell count, absolute lymphocyte count, platelet count, and heart rate, with manageable complication rates under close nursing monitoring.
What is known and what is new?
• Severe pertussis remains a major cause of infant morbidity and mortality, with no specific curative therapy currently available. Exchange transfusion has been reported in case series to alleviate hyperleukocytosis and improve oxygenation, but traditional methods carry notable risks.
• This study provides new evidence that a venous-venous closed system controlled by infusion pumps can serve as a safer, modified ET approach. It demonstrates that this method not only improves survival outcomes but also highlights the critical role of systematic nursing care in preventing complications.
What is the implication, and what should change now?
• Modified ET should be considered as an adjunctive therapy in infants with severe pertussis, especially those presenting with hyperleukocytosis, tachycardia, or pulmonary complications. Implementation requires thorough preoperative preparation, meticulous nursing observation, and prompt intervention for potential adverse events. Wider clinical adoption and multicenter prospective studies are warranted to validate these findings and to promote standardized protocols that may change current supportive-only management.
Introduction
Pertussis, also called whooping cough, featured with violent cough, is a highly contagious respiratory infection disease, and has become the leading cause of death from infectious disease among children (1). About 38% of pertussis cases occur in infants aged <6 months, and 71% in children aged <5 years old (2). Pertussis affects nearly 24 million children aged <5 years old per year, and leads to 160,000 deaths in this age group (2). According to a multicenter study, the direct severe pertussis-related hospitalization costs were over 1 million US dollars (USD) per year (3). Therefore, the effective treatment of pediatric pertussis is essential.
Exchange blood transfusion (ET), is considered as an alternative treatment for some diseases. ET was reported to improve the oxygenation of a 3-month-old infant hospitalized with pertussis pneumonia, hypoxemia, hyperleukocytosis, and pulmonary hypertension (4). Since the death of young infants with severe pertussis was associated with extreme leukocytosis, refractory pulmonary disease, and pulmonary hypertension (5,6), ET may be a novel treatment to improve the outcome of severe pertussis. Several case reports revealed that ET could prevent fatal outcomes of severe pertussis (7). In the traditional ET, the volume of blood exchange was controlled by manually withdrawing blood through an arterial line and reinfusing via a venous line, which often leads to complications such as infection, embolism, and electrolyte disturbances. In contrast, the modified ET used in our study employs a venous-venous closed system controlled by infusion pumps, which reduces these risks.
Since ET has not been widely used in severe pertussis children, its effects on the outcome of severe pertussis need further confirmation. In China, evidence regarding the effectiveness of modified exchange transfusion (ET) for severe pertussis remains limited. Therefore, the present study, conducted in a single tertiary center in south China, aimed to compare outcomes of infants with or without receiving modified ET and to summarize key nursing points in severe pertussis. We present this article in accordance with the STROBE reporting checklist (available at https://tp.amegroups.com/article/view/10.21037/tp-2025-411/rc).
Methods
Design
This case-control study was conducted in the intensive care unit (ICU) in Guangzhou Women and Children’s Medical Center from January 2018 to December 2019. Children diagnosed with severe pertussis were included. Pertussis was confirmed by clinical features and laboratory examinations. Severe pertussis was defined as patients with pertussis resulting in ICU admission and the need for advanced life support [defined as mechanical ventilation, vasoactive drugs, or extracorporeal membrane oxygenation (ECMO)]. The nasopharyngeal secretions of all participants were tested to have B. pertussis by polymerase chain reaction (PCR). Children with comorbidities (e.g., inherited metabolic diseases, severe immunodeficiency, neuromuscular diseases, and myelosuppression with hematologic malignancies) were excluded. Patients with incomplete data (discharged against medical advice or who died within 24 hours) were excluded (8). Severe pertussis children who underwent modified ET were enrolled as the modified ET group, while those receiving conservative treatment without modified ET were selected into the control group. The need for ET treatment was determined according to the doctors’ experience and high white blood cells (WBCs) combined with shortness of breath, and fast heart rate.
Nursing procedures for modified ET
Participants preparation
Participants’ previous medical history and physical condition, and their parents’ history of cough and expectations were assessed by nurses.
Preoperative preparation
Vascular channel choice: For the modified ET procedure in this study, a double-lumen central venous catheter was used. The internal jugular vein was the first choice, and the femoral vein was the second choice. This venous-venous closed system allowed both infusion of blood products and withdrawal of blood, thereby avoiding arterial puncture and reducing the risk of arterial complications. During modified ET, if invasive blood pressure monitoring was required, an arterial catheter (commonly in the radial artery) was connected to a pressure transducer and bedside monitor to continuously record arterial blood pressure.
Medicines and equipment: Based on the child’s body weight, blood products equivalent to 1–2 times the estimated circulating blood volume were prepared in advance. The medicines (heparin solution: 0.9% sodium chloride injection 250 mL + heparin 6,250 IU, epinephrine, and dexamethasone) and equipment (three infusion pumps, two pairs of blood transfusion pumps, one three-way connector tube, one standard intravenous infusion tube, and one closed chest drainage bottle) were prepared.
Personnel and environment: The child was placed in a single room with two nurses and one doctor to perform the procedure. One nurse performed modified ET, one nurse monitored vital signs and collected blood samples for tests, and the doctor was responsible for monitoring the process and managing complications.
Operative procedure
The following operative procedure of modified ET therapy was as per the Chinese version of Practical Neonatology, 5th Edition. The red blood cells (RBCs) and plasma were preheated to 36 ℃. Two pairs of blood transfusion pumps were connected to the double-lumen central venous catheter. RBC and plasma were transfused into the device simultaneously at a fixed ratio of 2:1, and two infusion pumps were used to precisely control the infusion rates. The output end was connected to the venous catheter through a three-way connector tube, where heparin solution was infused at 30 mL/h to maintain smooth blood flow and prevent coagulation. The other end was connected to a common intravenous infusion tube, which was connected to an infusion pump and then connected to a thoracic drainage device to collect the replaced blood and heparin solution. The output pump, input pump, and heparin pump were all adjusted to speed level ‘2’ on the infusion pump scale (corresponding to approximately 30 mL/h for heparin infusion), ensuring balanced inflow and outflow within the closed system. Generally, the duration of modified ET is controlled to be completed within 90–120 min. The process of modified ET was controlled to be strictly aseptic, and complications were closely monitored.
Nursing for operative complications
In the modified ET, the device used in this study was closed, and the input and output ends are automatically controlled by infusion pumps, which can reduce the occurrence of pollution, hypotension, and disorders of blood gas and electrolytes. Close monitoring of complications during the procedure and timely intervention could further reduce adverse events. The targeted nursing measures, defined as complication-specific nursing interventions, were as follows:
Hypotension
Avoid unstable capacity control. When hypotension occurred, adjustment of capacity was made immediately, and the speed of blood transfusion pump was confirmed or adjusted.
Bleeding/thrombus
Anticoagulant therapy during transfusion may increase the risk of bleeding or thrombosis. Therefore, coagulation function was closely monitored, and the heparin dosage was adjusted in a timely manner to reduce bleeding risk. If an embolism occurred in the output line, the infusion tubing was immediately replaced to restore blood flow.
Hypothermia
Life-threatening hypothermia can easily occur due to administering large amount of blood products. The blood products were preheated or warmed to 36 ℃ for modified ET, and body temperature were closely monitored during modified ET.
Allergic reaction
Before the procedure, each child’s allergy history was carefully assessed, and adequate amounts of cross-matched and safety-tested fresh frozen plasma were prepared in advance by the hospital blood bank and kept readily available at the bedside. If an allergic reaction occurred, the procedure was stopped immediately, and anti-allergic agents were promptly administered. In cases of anaphylactic shock, the 2015 pediatric protocol (9) was followed, and epinephrine and dexamethasone were prepared for emergency use.
Disorders of blood gas and electrolytes
During modified ET, hyperkalemia, low magnesium, low calcium, hypoglycemia, acidosis, and other complications were commonly seen. Blood gas, blood glucose, and electrolyte analysis would be performed every 30 min. Vital signs would be monitored closely for any changes.
Data collecting
Patients’ demographics (age, gender), clinical symptoms and signs (cough, fever, tachycardia, tachypnea, oxygen saturation, crackles, wheezing), laboratory indicators (WBC counts, absolute lymphocyte counts, platelet counts) and imaging examination (X-ray, echocardiography), and outcomes on discharge were collected, and various indicators of severe pertussis patients were compared after modified ET.
Statistical analysis
R Version 3.6.1 software was used to perform statistical analysis. The categorical data were described by frequencies and percentages. The data for the ET group and control group were compared by using Fisher’s exact test. The t-test was used to measure the changes of various indicators after modified ET. Statistical significance was set at P<0.05.
Ethical considerations
This study was approved by the Research Ethics Committee of Guangzhou Women and Children’s Medical Center (approval No. [2021]051A01). All data were collected anonymously. Written informed consent was obtained from the parents or legal guardians of all participants. This study was conducted in accordance with the Declaration of Helsinki and its subsequent amendments.
Results
Baseline characteristics of patients
A total of 31 patients with severe pertussis were involved, with 19 patients in the control group and 12 patients in the ET group. A total of 29 (93.5%) had cough, 23 (74.2%) had fever, 18 (58.1%) had lower oxygen saturation, and 17 (54.8%) had tachycardia. Hyperleukocytosis was observed in 12 (38.7%), pulmonary hypertension in 13 (41.9%), and pneumonia on X-ray in 26 (83.8%), and patients with pneumonia tended to have a more severe pneumonia (see Figure 1). Table 1 presents the detailed baseline information.
Table 1
| Variable | Total | ET group (n=12) | Control group (n=19) | P value |
|---|---|---|---|---|
| Demographics | ||||
| Male | 15 | 6 | 9 | 0.89 |
| Age (<3 months) | 27 | 10 | 17 | 0.62 |
| Preoperative symptoms and signs | ||||
| Cough | 29 | 12 | 17 | 0.25 |
| Fever | 23 | 10 | 13 | 0.36 |
| Tachycardia (heart rate >180/min, ≤1 year) | 17 | 9 | 8 | 0.07 |
| Tachypnea (respiratory rate >70/min, ≤1 year) | 14 | 8 | 6 | 0.06 |
| Oxygen saturation <90% | 18 | 8 | 10 | 0.44 |
| Crackles | 29 | 12 | 17 | 0.25 |
| Wheezing | 11 | 5 | 6 | 0.57 |
| Preoperative laboratory indicators | ||||
| White blood cells >50.0×109/L | 12 | 5 | 7 | 0.79 |
| Platelet >600×109/L | 10 | 4 | 6 | 0.92 |
| Absolute lymphocyte >20×109/L | 12 | 5 | 7 | 0.79 |
| Preoperative radiological findings | ||||
| X-ray | ||||
| Pneumonia | 26 | 11 | 15 | 0.35 |
| Pleural effusion | 11 | 5 | 6 | 0.57 |
| Echocardiography | ||||
| Pulmonary hypertension | 13 | 5 | 8 | 0.98 |
| Outcome | ||||
| Dead | 12 | 2 | 10 | 0.045* |
*, statistically significant. ET, exchange blood transfusion.
Comparison of outcomes and indicators
Two (16.7%) patients died after the modified ET, while 10 (52.6%) patients died in the control group, with significant differences in the outcomes of the two groups (P<0.05). As Figure 2 presents, WBC count, absolute lymphocyte count, platelet count, and heart rate after modified ET were significantly lower than before in the ET group (P<0.05).
In the ET group, the incidence of complications was 33.3% (4/12), including two cases of embolisms in the arterial output end and two cases of hypotension. Infusion tubes were timely replaced, and capacity was immediately adjusted to solve the problem. Other complications, such as bleeding, hypothermia, allergic reaction, and disorders of blood gas and electrolytes, did not occur.
Discussion
This case-control study presents a general practice perspective of the effects of modified exchange blood transfusion therapy on severe pertussis.
The occurrence of severe pertussis among children
In this study, the total mortality rate of severe pertussis children was 12/31 (38.7%), much greater than 5% reported by an observational study of severe pertussis in 100 infants 120 days of age (6). This high mortality indicated the necessity of effective treatments to improve outcome. Whereas, there is no specific drug that can quickly cure severe whooping cough. Current treatments of severe pertussis are mainly supportive therapy, including mechanical ventilation, inhalation of nitric oxide (NO), exchange blood transfusion, and extracorporeal membrane oxygenation (ECMO) (3,10).
Effects of exchange blood transfusion on improving severe pertussis
Some studies revealed that exchange blood transfusion is a novel treatment for severe pertussis in infants (11), and has been more frequently used in recent years. This treatment can reduce excessive leukocytosis and pertussis toxin, which are closely associated with severe pertussis (12,13). Notably, pertussis toxin can alter the vagal control of the heart rate by inhibiting the activity of G-proteins (13,14). In this study, infants’ heart rate significantly decreased after receiving modified ET, indicating that ET might decrease heart rate by reducing pertussis toxin. Though Cherry et al.’s data (6) were insufficient to address the efficacy of the ET procedure, the significant lower mortality rate of the modified ET group in this study supported effectiveness of modified ET on severe pertussis infants.
Significance of exchange blood transfusion from the perspective of nursing
The capacity control of traditional ET depends on the artificial extraction of blood from the artery, which is prone to complications such as infection, thrombus, and disorders of blood gas and electrolytes. In our study, the modified ET has infusion pumps at both the input and output to automatically control capacity, which is convenient for maintaining aseptic and preventing pollution. Although the occurrence rate of operative complications was 33.3%, infusion tubes were timely replaced, and capacity adjustments were made immediately to handle the problems. Due to close attention to preoperative preparations, observation of complications, and timely intervention (e.g., preheating the blood products, detecting the coagulation function, preparing the fresh plasma, epinephrine, and dexamethasone), the ET group patients’ WBC counts, absolute lymphocyte counts, and heart rates significantly decreased without any occurrence of severe hypotension, thrombus, bleeding, hypothermia, allergic reactions, or disorders of blood gas and electrolytes. Therefore, modified ET can be an effective treatment for severe pertussis patients with careful nursing.
Limitations
There are some limitations in this study. Firstly, the sample size in this study was small, and from only one tertiary hospital in south China. Therefore, the results should be taken with caution and the results may not be able to generalized to other countries or regions. Multi-center studies with larger sample size are need to be conducted to address this issue. Secondly, the case-control design of this study could not control all factors that might influence the effects of the modified ET. Therefore, rigorous and prospective studies with multi-centered larger sample are needed to confirm our findings in the future.
Relevance for clinical practice
Owing to the serious conditions of severe pertussis patients, it is important for nurses and doctors to realize the risks during modified ET, and make full preparation in advance. Meanwhile, careful observation of complications and timely intervention can help reduce complications and improve outcomes. This study can provide new insight into nursing for severe pertussis patients during modified ET.
Conclusions
This case-control study performed the modified ET on children with severe pertussis. The modified ET was effective in improving severe pertussis and could decrease the mortality. The WBC count, absolute lymphocyte count, platelet count, and heart rate significantly decreased after the modified ET. Paying much attention to preoperative preparations, observation of complications, and timely intervention can help reduce complications.
Acknowledgments
We would like to thank all patients and their families involved in this study.
Footnote
Reporting Checklist: The authors have completed the STROBE reporting checklist. Available at https://tp.amegroups.com/article/view/10.21037/tp-2025-411/rc
Data Sharing Statement: Available at https://tp.amegroups.com/article/view/10.21037/tp-2025-411/dss
Peer Review File: Available at https://tp.amegroups.com/article/view/10.21037/tp-2025-411/prf
Funding: This study was supported by
Conflicts of Interest: All authors have completed the ICMJE uniform disclosure form (available at https://tp.amegroups.com/article/view/10.21037/tp-2025-411/coif). The authors have no conflicts of interest to declare.
Ethical Statement: The authors are accountable for all aspects of the work in ensuring that questions related to the accuracy or integrity of any part of the work are appropriately investigated and resolved. This study was approved by the Research Ethics Committee of Guangzhou Women and Children’s Medical Center (approval No. [2021]051A01). All data were collected anonymously. Written informed consent was obtained from the parents or legal guardians of all participants. This study was conducted in accordance with the Declaration of Helsinki and its subsequent amendments.
Open Access Statement: This is an Open Access article distributed in accordance with the Creative Commons Attribution-NonCommercial-NoDerivs 4.0 International License (CC BY-NC-ND 4.0), which permits the non-commercial replication and distribution of the article with the strict proviso that no changes or edits are made and the original work is properly cited (including links to both the formal publication through the relevant DOI and the license). See: https://creativecommons.org/licenses/by-nc-nd/4.0/.
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