Table 2: Outcomes measured. Table 1: Intrapleural alteplase instillation therapy protocol

Transcription

1

2 ORIGINAL RESEARCH ARTICLE Intrapleural F brinolytic Therapy with Alteplase in Empyema Thoracis in Children conducted in the Department of Pediatric critical care and Pulmonology unit at our institution from May 2012 to April The diagnostic criteria for empyema thoracis were: Presence of pleural effusion on clinical, radiological examination, and aspiration of purulent pleural fluid from the thoracic cavity. After IRB approval for the pilot study, all children diagnosed with empyema thoracis as per above criteria from the age of 1 month to 18 years were included in the study after informed consent. Children who showed clinical improvement and lung expansion within hours of ICD placement, children with significant pleural thickening with organized collections (stage III empyema) on ultrasound chest, were not given alteplase therapy and were excluded from the study. Complete blood count, prothrombin time (PT)/ International normalized ratio (INR), C-reactive protein, erythrocyte sedimentation rate (ESR) and blood culture were sent on all patients. Pleural fluid cytology, biochemistry, gram stain, acid fast bacillus stain, and cultures were sent. Chest radiograph and ultrasound were done. Intercostal tube (ICD) was placed in cases of empyema, loculated effusion and exudative collection based on pleural fluid examination. Chest radiograph and ultrasound were repeated after hour of placement of ICD. Intrapleural alteplase therapy was given to patients with persistent symptoms with septated, loculated collections evident on ultrasound chest or aspiration of intrapleural pus. All children were managed with intravenous ceftriaxone and cloxacillin as initial therapy along with other supportive therapy as indicated. However in 6 cases, due to non-availability of cloxacillin, intravenous vancomycin was used. Methods (Intrapleural alteplase instillation therapy protocol) and outcomes measured are listed in table 1 and 2. Table 1: Intrapleural alteplase instillation therapy protocol Prerequisite: INR < 1.5 and platelet count > 50000/ mm 3 Procedure 1. Injection alteplase 4 mg was diluted with 50 ml NS and instilled through ICD. Chest tube was kept clamped for 1 hour and then opened. 2. Intrapleural alteplase was given once daily for maximum of 3 days. 3. Children were monitored for fever and respiratory distress. 4. Chest radiograph was done 24 hours after 2 nd or 3 rd dose as indicated by clinical improvement or deterioration. Table 2: Outcomes measured S No. Primary Secondary 1 Clinical Improvement Average per day ICD output 2 Lung Expansion Any side effects (bleeding, pain, allergic reaction, respiratory distress) 3 Duration of ICD (Days) 4 Length of Hospital stay (Days) ICD - Intercostal tube Tube removal and discharge Intravenous antibiotics were continued till 48 hours of afebrile period. The ICD was removed when there was no drainage or minimal drainage from ICD (<20 ml/day) along with clinical improvement and lung expansion on chest radiograph. The criteria for discharge included: absence of fever for at least 48 hours, stable clinical condition and good lung expansion. Oral antibiotic therapy were completed for further 10-14days after discharge. Failure of therapy Failure of therapy was defined if there was no improvement in clinical condition or persistence of intrapleural collection or persistent lung collapse. No improvement in clinical condition was defined as persistence of fever spikes ( 100.4*F) and poor oral intake. In case of failure of therapy surgical intervention (VATS/Open thoracotomy) was performed by pediatric surgeon. Results A total of 17 children were admitted with empyema thoracis. Two cases showed clinical improvement with lung expansion after ICD alone and 2 had stage III empyema, all 4 cases were excluded from the study. A total of 13 patients were given intrapleural alteplase based on selection criteria. Median age was 3years and ranged from 11 month to 14 years. Male to Female ratio was 1:1.16. Right and left sided empyema was seen in 6 cases each while one case had bilateral involvement. All children presented with fever ranging from 2-22 days with median of 10 days. Cough and respiratory distress (RD) were seen in 92% (11/13) of cases. Duration Vol. 1 - No.3 July - September JOURNAL OF PEDIATRIC CRITICAL CARE

3 ORIGINAL RESEARCH ARTICLE Intrapleuralfi brinolytic Therapy with Alteplase in Empyema Thoracis in Children of RD ranged from 1-20 days with median 5 days. Chest pain and abdominal pain were seen in 15.4 % (2/15) cases. Mean Hemoglobin (Hb) at presentation was 9±1gm/dl and 85% of cases had Hb<10gm/dl. High total leucocyte count was seen in 77% (10/13) of patients and one patient had leucopenia. Neutrophilic leucocytosis (Neutrophils >65%) was seen in 77% of cases. Pleural fluid revealed frank pus in 70% of cases and pleural fluid sugar was < 40mg in 92% of cases. Pleural fluid revealed bacterial growth in 38.4% of cases (5/13), out of which 3 were Staphylococcus aureus and 1 each Burkholderia cepacia and Acenitobacter Baumanii. All blood cultures were negative except one child who had positive blood culture growing Burkholderia cepacia. INR was >1.5 in 2 cases at presentation which was corrected over next 48hours.. Platelet count was above 50000/cmm in all cases. Chest radiograph revealed pleural effusion and parenchymal opacities in all cases (Table 3). Mediastinal shift was seen 61.5% (8/13) and pyopneumothorax was seen in 15.4% (2/15). Ultrasound of chest revealed collapsed lung in all cases. Sepations/Loculated collections were seen in 77% (10/13) cases. Pericardial effusion was seen in 15.4% (2/15) and one case had multiple liver abscesses. Contrast enhanced computed tomography (CECT) chest was done in total of 7 cases out of which 4 were done at outlying hospitals with CECT films and reports brought by parents on day of admission to our hospital. Clinical improvement and Lung expansion Clinical and radiological improvement was seen in 84.6% (11/13) cases. Fever subsided within 5 days in 54% patients with median of 4 days (ranging 2-8days). Respiratory distress settled in median of 5 days (ranging 2-7 days). ICD days and Hospital stay ICD days were 6.63±1.8 (Mean ± SD) days. ICD days after starting alteplase were 3.45 ± 1.03 (Mean ± SD). ICD manipulation was not required in any case. Mean hospital stay was11.27 ± 4.14 (Mean ± SD) days in successful cases. Mean hospital stay in all patients including failure case was 13±5.75 (Mean ± SD) days. Average Flow (ml/day) from ICD Average flow per day before alteplase was 64.5 ± 65 ml/day which increased to ± ml/day with intrapleuralalteplase. (P value 0.006) Adverse effects No major adverse effects were noted. Although all cases had some pain, in most cases manageable by oral analgesics. Only 3(23%) children had severe pain requiring intravenous analgesics. Most cases (77%) had minor bleeding in the form of blood tinged discharge without causing hemodynamic compromise or need for transfusion. Failure of therapy Persistent fever, distress and lung collapse was seen in 15.4% (2/13) cases. Both underwent CECT (Contrast Enhanced computerized tomogram) chest which revealed thick enhancing pleural thickening apart from collapse-consolidation of lung. VATS was done in one and another case required open decortication. Antibiotics and supportive therapy All children received intravenous antibiotics. Intravenous ceftriaxone and cloxacillin, or ceftriaxone and vancomycin were started in 46% (6/13) cases and one case was continued on Meropenem/vancomycin. Antibiotics were changed in only 2 cases: one changed as per culture sensitivity report and in one case was upgraded due to clinical deterioration. All cases received oxygen and mechanical ventilation was required in 23% (3/13) cases. Discharge All children were discharged after clinical and radiological improvement. None of the cases had chest deformity at the time of discharge. Chest radiographs at discharge showed resolution of effusion with complete lung expansion in all cases. None of the cases had mediastinal shift, rib crowding or scoliosis on chest radiograph at the time of Vol. 1 - No.3 July - September JOURNAL OF PEDIATRIC CRITICAL CARE

4 ORIGINAL RESEARCH ARTICLE Intrapleural F brinolytic Therapy with Alteplase in Empyema Thoracis in Children Table 3: Radiological Findings upon Admission and Discharge, No. (%) X-ray findings At admission At Discharge At Discharge With failure cases Pleural effusion 13(100%) 0 0 Parenchymal 13(100%) 3/11(27%) 5/13(38.4%) opacities Pyopneumothorax 2/13(15.4%) 0 0 Mediastinal shift 8/13(61.5%) 0 0 Pleural thickening 0 3/11(27%) 5/13(38.4%) Rib crowding/ Scoliosis discharge. Figures 1-3 show examples of serial X rays from 3 randomly selected patients who recieved therapy with aleteplase. Chest radiographs showed parenchymal opacities and pleural thickening in 27% (3/11) of children treated with alteplase therapy alone and was seen in 38.4% (5/13) in all cases including the failed cases (Table 3). Follow up Chest radiographs after 2 weeks in these patients revealed complete resolution (Figure 1-3 shows serial chest radiographs of 3 randomly selected patients who received alteplase therapy). Figure 1: Serial chest x ray 1a: AT admission: Left side white out; 1b: 48 hours after ICD: Collapsed left Lung with persistent collection; 1c: Post 3rd dose Alteplase: Expanded left lung with residual collection; 1d: At discharge-day 9: Expanded left Lung with pleural thickening; 1e: After 2 weeks follow up: Complete resolution Figure 2: Serial chest x ray 2a: AT admission: Left Pyopneurnothorax; 2b: 24 hours after ICD: Persistent Pyopneurnothorax; 2c: Post 2nd dose Alteplase: Expanded left lung with residual Pyopneurnothorax; 2d: At discharge-day 9: Fully Expanded left Lung; 2e: After 2 weeks follow up: Complete resolution Figure 3: Serial chest x ray 3a: AT admission: Left Pleural effusion; 3b: 48 hours after ICD: Persistent Left collection with underlying lung collapse; 3c: Post 3rd dose Alteplase: Fully Expanded left lung; 3d: At discharge-day 9: Complete Resolution Vol. 1 - No.3 July - September JOURNAL OF PEDIATRIC CRITICAL CARE

5

6