Exchange transfusion for hyperleucocytosis in a critical case of pertussis

Meeting abstracts from the 15th international conference on neonatal and childhood pulmonary vascular disease

The Cardio-Obstetrics Patient and the Cardiothoracic Anesthesiologist

Descriptive patterns of severe chronic pulmonary hypertension by chest radiography

Hypoxia causes pulmonary vasoconstriction. Regional hypoxic vasoconstriction improves the matching of perfusion to alveolar ventilation. Global hypoxic vasoconstriction increases right ventricular afterload. The hypoxic pulmonary pressor response is universal in mammals and in birds, but with considerable interspecies and interindividual variability. Chronic hypoxia induces pulmonary hypertension in proportion to initial vasoconstriction. Prolonged hypoxic exposure is also associated with an increase in red blood cell mass, which aggravates pulmonary hypertension by an increase in blood viscosity. Hypoxic pulmonary hypertension in humans is usually mild to moderate, but pulmonary vascular pressure-flow relationships are steep, which corresponds to a substantial afterload on the right ventricle during exercise. A partial recovery of 10-25% of the hypoxia-induced decrease in maximal oxygen uptake has been reported with intake-specific pulmonary vasodilating interventions. Hypoxia has been reported to decrease myocardial fibre contractility in vitro. However, the acutely hypoxic right ventricle remains able to preserve the coupling of its contractility to increased afterload in intact animals. Echocardiographic studies of the right ventricle in healthy hypoxic human subjects show altered diastolic function, but systolic function that is preserved or even increased acutely and slightly depressed chronically. These findings are more pronounced in patients with chronic mountain sickness. Their clinical significance remains incompletely understood. Almost no imaging studies of right ventricular function have been reported in a minority of subjects who develop severe pulmonary hypertension and clinical right ventricular failure in hypoxia. No imaging studies of right ventricular function during hypoxic exercise in normal subjects are yet available. Thus, while it is plausible that the right ventricle limits exercise capacity in hypoxia, this still needs to be firmly established.

Introduction: Malignant pertussis characterized by severe leukocytosis, pneumonia, pulmonary hypertension (PH), and multisystem organ failure (MSOF) has been reported to have a high mortality. The presence of PH was reported in 75% of fatal cases as compared to 6% in survivors. Timely leukoreduction (LR) therapy may help by reducing leukocyte aggregates from pulmonary circulation, washing out mediators, and by improved viscosity. We present a case of malignant pertussis who benefited from LR via whole blood exchange transfusion (ET). A 7-week-old Hispanic female was admitted for suspected bronchiolitis. Baseline White Blood Cell (WBC) count was 12.6x10^3/mcL. Echocardiography was normal with no evidence of PH. She developed worsening respiratory distress, apneic spells prompting transfer to our Pediatric Intensive Care Unit. Chest x-ray revealed bilateral patchy infiltrates and hyperinflation. WBC count was 46.4x10^3/mcL. Pertussis was confirmed by polymerase chain reaction testing. She rapidly deteriorated, requiring escalating ventilator support. PH unresponsive to inhaled nitric oxide therapy was diagnosed next day. Her WBC count increased to 90.7x10^3/mcL at 42 hours of admission. A 1.5 volume ET was performed. Post-ET, WBC count decreased to 22x10^3/mcL. Her arterial oxygen (O2) pressure to fraction of inspired O2 concentration ratio (P/F ratio) dramatically increased from 110 to 217 in 4 hours. Her WBC count increased again to 36 x10^3/mcL but at a much slower rate and then stabilized at around 25x10^3/mcL. She was extubated on day eight of PICU stay and discharged home on day 34. LR therapy has shown variable success. No survival benefit was reported in one prospective randomized observational study (14 in LR group compared to 25 controls), but patient selection and timing of initiation of LR was not standardized. Another center using an algorithmic approach to LR reported 90% (n=10) survival compared to 55 % survival in a historical cohort (control:n=9). We believe that timely ET prior to MSOF halted rapid progression of illness and led to improved oxygenation in our patient. ET prior to MSOF may be a key factor in the survival from this devastating disease.

Objective To evaluate the value of noninvasive monitoring of pulmonary arterial pressure in the children with severe pneumonia and respiratory failure. Methods A prospective study was adopted to investigate 69 patients who suffered from severe pneumonia and respiratory failure in Pediatric Intensive Care Unit in Shanghai Children's Hospital from June 2013 to December 2013 were involved in this study, except for heart disease.The pulmonary arterial pressure (PAP) and cardiac function were monitored by using bedside color doppler ultrasound cardiogram, such as PAP, cardiac index (CI), left ventricle ejection fraction(LEFT), and heart early diastolic filling velocity maximum/heart late diastolic filling velocity maximum (E/A ratio). They were divided into 2 groups according to PAP, one group as pulmonary arterial pressure normal group, the other group as pulmonary arterial hypertension(PAH) group, and the impact of the PAP on the prognosis and mechanical ventilation was assessed.Milrinone[0.5 μg/(kg·min)]were given the patients who were combined with pulmonary hypertension, and the PAP and cardiac function before using Milrinone and 24 h, 48 h and 72 h after giving medicine was observed. Results Among 69 cases, 40 cases were male and 29 cases were female, age ranging from 2 months to 12 years old, and the weight range was (14.3±8.9) kg.The pe-diatric critical illness score(PICS) was 70.5±9.6, and the pediatric risk of score mortalityⅢ was 13.5±5.0.Among 69 cases, 46 cases had pulmonary arterial hypertension, 38 cases of them experienced mechanical ventilation, and 9 cases died.Among 23 cases who had no pulmonary arterial hypertension, only 8 cases experienced mechanical ventilation.There was a significant difference in the mechanical ventilation rate and mortality between two groups(χ2=15.78, P 0.05). However, 9 cases of them did not show any response to Milrinone, and in the end they couldn't live without mechanical ventilation, they died. Conclusions Noninvasive pulmonary arterial pressure monitoring could be beneficial in judging patient's condition and assessing prognosis of children with severe pneumonia and respiratory failure, and milrinone could decrease PAP. Key words: Pulmonary arterial hypertension; Color doppler ultrasound cardiogram; Pneumonia, severe; Respi-ratory failure; Milrinone; Child

To identify risk factors for severe pertussis and assess the efficacy of exchange transfusion in children. We analyzed pediatric pertussis cases, comparing mild and severe presentations using hospital data on demographics, symptoms, lab findings, echocardiography, and complications, and employed ROC analysis to determine severe pertussis risk factors. Our study analyzed 119 mild and 64 severe pertussis cases, with severe cases characterized by earlier onset, spasmodic cough, shortness of breath, and rales. Risk factors for severity included lack of DTaP vaccination and pulmonary hypertension. Severe cases also showed higher WBC and lymphocyte counts and more mixed infections. Logistic regression identified shortness of breath, no DTaP, younger age, and high WBC as severity predictors (P < 0.05). ROC analysis predicted severity with age < 3.68 months and WBC > 27.93 × 109/L (AUC = 0.606, 0.725; P < 0.05). Exchange transfusion in patients with rising WBC and shortness of breath normalized pulmonary hypertension and led to recovery. Clinicians should closely monitor unvaccinated children with shortness of breath, onset before 3.68 months, and WBC > 27.93 × 109/L for severe pertussis risk. Exchange transfusion is advised for those with WBC > 40 × 109/L and pulmonary hypertension, showing significant therapeutic benefit. This study delineates four key predictors of severe pertussis in children: younger age, lack of DTaP vaccination, shortness of breath, and elevated white blood cell (WBC) counts. We establish WBC > 27.93 × 109/L as a robust quantitative biomarker for severity prediction (AUC = 0.725), providing clinicians with an objective threshold to prioritize intensive monitoring and intervention. Exchange transfusion demonstrates efficacy in reducing WBC levels and resolving pulmonary hypertension in critical cases. These findings reinforce the imperative of DTaP vaccination to prevent severe disease and inform evidence-based management protocols.

Since the last World Symposium on Pulmonary Hypertension in 2008, we have witnessed numerous and exciting developments in chronic thromboembolic pulmonary hypertension (CTEPH). Emerging clinical data and advances in technology have led to reinforcing and updated guidance on diagnostic approaches to pulmonary hypertension, guidelines that we hope will lead to better recognition and more timely diagnosis of CTEPH. We have new data on treatment practices across international boundaries as well as long-term outcomes for CTEPH patients treated with or without pulmonary endarterectomy. Furthermore, we have expanded data on alternative treatment options for select CTEPH patients, including data from multiple clinical trials of medical therapy, including 1 recent pivotal trial, and compelling case series of percutaneous pulmonary angioplasty. Lastly, we have garnered more experience, and on a larger international scale, with pulmonary endarterectomy, which is the treatment of choice for operable CTEPH. This report overviews and highlights these important interval developments as deliberated among our task force of CTEPH experts and presented at the 2013 World Symposium on Pulmonary Hypertension in Nice, France.

Going Home with a Patent Ductus Arteriosus: Is it Benign?

Riociguat, an oral soluble guanylate cyclase stimulator, has been approved for use in adults with pulmonary arterial hypertension (PAH) and chronic thromboembolic pulmonary hypertension. However, there is limited data on its therapeutic use in children. We report the case of two infants with severe suprasystemic pulmonary hypertension who were successfully treated with riociguat after failure to wean off inhaled nitric oxide (iNO) despite combination PAH therapy. Case 1 is a 6-month-old term male with TBX4 deletion who presented with severe hypoxemic respiratory failure and severe PAH immediately after birth. Initial cardiac catheterization showed PVRi 15.5 WU*m2. Marked hypoxemia and PAH persisted despite aggressive therapy with sildenafil, bosentan, intravenous treprostinil, and milrinone. The infant required high doses of inhaled nitric oxide (60 ppm) and manifested significant post-ductal hypoxemia and hemodynamic instability with any attempt at weaning. After discontinuation of sildenafil, initiation, and very slow uptitration of riociguat, the patient was able to maintain hemodynamic stability and wean from nitric oxide over 6 weeks with persistently severe but not worsened pulmonary hypertension. Case 2 is a 4-month-old term male with compound heterozygous SLC25A26 mutation and severe pulmonary hypertension. Initial cardiac catheterization showed PVRi 28.2 WU*m2. After uptitration of sildenafil, bosentan, and IV treprostinil, serial echocardiograms continued to demonstrate near-systemic pulmonary hypertension. He failed multiple attempts to wean off typical doses of iNO (10-20 ppm) over the following weeks with tachypnea, hypoxemia, and worsening pulmonary hypertension on echocardiogram despite continued aggressive combination targeted therapy. After a 24-h sildenafil washout, he was initiated and uptitrated on riociguat with concomitant, successful wean of nitric oxide over one week that was well tolerated. No serious adverse effects in the titration period were observed. Riociguat may be considered as an adjuvant therapeutic agent in selected children with severe PAH who are poorly responsive to sildenafil therapy and unable to wean from iNO.

Left ventricle is better suited as pulmonary ventricle in simple transposition with severe pulmonary hypertension

A New Classification of Pulmonary Hypertension

Pertussis, or "whooping cough," is a highly communicable disease caused by the coccobacillus Bordetella pertussis. Pertussis remains one of the most common causes of death from infectious diseases worldwide. We describe a 5-week-old infant girl who presented with severe pertussis infection associated with extreme leukocytosis and required prolonged extracorporeal membrane oxygenation (ECMO). Nitric oxide therapy resolved the pulmonary hypertension, and she was successfully weaned from ECMO and discharged home after 3 months. We report successful application of ECMO for severe pertussis-induced respiratory failure despite multiple grave prognostic indicators (<1 year age, leukocytosis, pulmonary hypertension) and discuss the role of extracorporeal life support in treating pertussis.

In patients with severe pulmonary arterial hypertension, subcutaneous or catheter-based intravenous application of prostanoids carries a risk of local side effects or systemic infections, which limits their use and acceptance. Recently, a fully implantable pump for continuous application of intravenous treprostinil was approved in Germany. However, surgery is a major risk for patients with severe pulmonary arterial hypertension. The purpose of this study was to investigate the safety of a fully implantable pump inserted under local or general anesthesia in patients with severe pulmonary hypertension. All patients with pulmonary hypertension undergoing pump implantation for the continuous application of intravenous treprostinil were included from two German centers. Surgery was performed under local or general anesthesia according to the protocol of the recruiting center. Intra-operative safety and in-hospital complications were analyzed for the two different implantation regimens. In total, 51 patients were included. No major intra-operative complications were recorded. During the observation period, two patients died of progressive right heart failure, and two patients required treatment in the intensive care unit for acute right heart decompensation and respiratory failure. In total, major complications occurred in 8 out of 51 patients. Our observational study provides preliminary evidence supporting the procedural safety of a fully implantable pump inserted under local or general anesthesia for patients with severe pulmonary hypertension. The observation of major complications in a subset of patients requires extensive pre- and post-operative assessments. Future trials are required to provide further evidence for the long-term safety and efficacy of the pump using this approach.

It is proposed that severe leucocytosis mainly contributes to pulmonary hypertension by blocking pulmonary capillaries and restricting blood flow. Exchange transfusion (ET) in pertussis has been demonstrated as a safe and useful technique for depleting the leucocyte mass. We aim to discuss four cases of pertussis-induced respiratory distress and the effectiveness of ET in such a setting. We conducted a retrospective case series at the Infectious Disease Department of Children's Hospital 2 in Ho Chi Minh City, Vietnam, and included four pertussis patients that were confirmed by PCR tests on respiratory secretions, presented with severe leucocytosis and respiratory distress and required mechanical ventilation. Among the included patients, three underwent a double volume ET for leucodepletion, two of whom were discharged after the procedure with proper vitals and laboratory test results. On the other hand, one patient died despite ET, performed late in the course of the disease. Exchange transfusion was not performed in the last patient who died as well. Early ET may be a useful and rapid life-saving treatment in children with critical pertussis and severe leucocytosis before cardiopulmonary complications appear.