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Sequential Organ Failure Assessment Predicts the Outcome of SCT Recipients Admitted to Intensive Care Unit

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Sequential Organ Failure Assessment Predicts the Outcome of SCT Recipients Admitted to Intensive Care Unit Bone Marrow Transplantation (2010) 45, 682–688 & 2010 Macmillan Publishers Limited All rights reserved 0268-3369/10 $32.00 www.nature.com/bmt ORIGINAL ARTICLE Sequential Organ Failure Assessment predicts the outcome of SCT recipients admitted to intensive care unit K Gilli1, M Remberger2, H Hjelmqvist1,3, O Ringden2,4 and J Mattsson2,4 1Department for Anaesthesiology and Intensive Care Medicine, Karolinska Institutet, Karolinska University Hospital, Huddinge, Stockholm, Sweden; 2Department of Clinical Immunology, Karolinska Institutet, Karolinska University Hospital, Huddinge, Stockholm, Sweden; 3Department of Clinical Science, Intervention and Technology (CLINTEC), Karolinska Institutet, Karolinska University Hospital, Huddinge, Stockholm, Sweden and 4Center for Allogeneic Stem Cell Transplantation, Karolinska Institutet, Karolinska University Hospital, Huddinge, Stockholm, Sweden We analyzed all patients undergoing allogeneic stem cell Introduction transplantation (ASCT) and transferred to the intensive care unit (ICU) from January 1995 to December 2005. The question if and when patients undergoing allogeneic stem During this period, 661 patients underwent ASCT at our cell transplantation (ASCT) should be transferred to an center. A total of 91 patients were admitted to the ICU. intensive care unit (ICU) is controversial. Several variables Median time from ASCT to ICU admission was 69 days have been associated with mortality in ASCT patients (À24 to 1572) and median stay at the ICU was 4 transferred to the ICU. Most common are patients requiring (1–60) days. The survival after transfer to the ICU at day mechanical ventilation, multiorgan failure and shock.1 100 and at 1 year was 22 and 16%, respectively. Median Despite the poor prognosis, survival after ICU care has been Sequential Organ Failure Assessment (SOFA) score reported.2–4 Since 1998, the survival of ASCT patients treated was 10 (1–17). Patients with SOFA score o8(n ¼ 18) in the ICU has improved, probably attributed to improve- had a 44% survival compared with 17% with SOFA score ments in ASCT treatment, patient selection and ICU 8–11 (n ¼ 30) and no survival with SOFA score 411 management.1 At the ICU, more sophisticated ventilation (n ¼ 20) (P ¼ 0.0002). None of the 14 retransplanted strategies have been developed,5 such as invasive and patients survived compared with 31% among patients noninvasive ventilation (NIV), and early goal-directed after first ASCT (P ¼ 0.006). Patients receiving TBI had therapy (EGDT).6 The latter means that patients should be a lower survival compared with patients treated with stabilized to normal physiological level as soon as possible at chemotherapy only (14 vs 45%, P ¼ 0.02). Patients the ICU. Reduced-intensity conditioning (RIC) regimens needing vasopressor support had a worse survival, 15 vs before ASCT have resulted in less toxicity.7 Molecular 41%, compared with patients without vasopressor treat- monitoring, more effective prophylaxis and preemptive ment (P ¼ 0.01). In multivariate analysis of death, SOFA treatment strategies of various infections have been developed score was the only significant factor (Po0.001). In during the past decade, improving survival after ASCT.8,9 conclusion, SOFA score predicted prognosis in ASCT Traditional prognostic systems such as acute physiological patients treated at the ICU. and chronic health evaluation (APACHE) have shown limited Bone Marrow Transplantation (2010) 45, 682–688; value in ASCT patients.1 APACHE II underestimated survival doi:10.1038/bmt.2009.220; published online 31 August 2009 in patients with scores less than 35, and could only be used to Keywords: SOFA; intensive care unit; SCT; allogeneic; predict 100% mortality when it exceeded 45.10 Sequential APACHE; survival Organ Failure Assessment (SOFA) showed good correlation to prognosis in other patient groups.11–13 The primary aim of this study was to analyze the incidence and outcome of all ASCT patients transferred to the ICU at our center between 1995 and 2005. The secondary aim was to find a tool to monitor the prognosis of ASCT patients admitted to the ICU. A valid prognostic factor for these patients may be useful in deciding whether an ICU treatment should be started and also whether ICU therapy should be discontinued in deteriorating patients. Correspondence: Dr J Mattsson, Department of Clinical Science, Center for Allogeneic Stem Cell Transplantation, Karolinska Institutet, Patients and methods Karolinska University Hospital, Huddinge, Stockholm SE-141 86, Sweden. E-mail: [email protected] Patients Received 5 February 2009; revised 8 July 2009; accepted 10 July 2009; A total of 661 patients received ASCT at Karolinska published online 31 August 2009 University Hospital, Huddinge between 1 January 1995 SOFA predicts outcome of ICU care after SCT K Gilli et al 683 Table 1 Characteristics of the 91 patients treated at ICU GVHD prophylaxis A total of 73 patients received a combination of CsA and All patients MTX as GVHD prophylaxis.16,17 In the absence of GVHD, Diagnoses CsA was discontinued after 6 months for patients who Non-malignant 9 received a matched unrelated donor or mismatched grafts, Acute leukemia 43 and after 3–4 months in the case of sibling transplant- Chronic leukemia 17 18 Other malignancy 15 ations. For patients with non-malignant disease, immu- Solid tumor 7 nosuppressive treatment was discontinued within 2 years. Disease stage (early/late) 42/44 Previous SCT 14 (15%) Supportive care During the pancytopenic phase, all patients received Age 34 (1–67) prophylactic treatment with oral ciprofloxacin (500 mg Children o18 years 26 (29%) twice daily), fluconazole (100 mg daily) and nystatin 9 Sex (M/F) 51/40 (200 000 IU, 4 times daily) until ANC exceeded 0.5 Â 10 / liter. Details regarding supportive care were published Donor earlier.8 HLA-id related 31 MUD 46 Mismatched 14 Donor sex (M/F) 49/39 ICU scoring systems Donor age 37 (0–71) Patients younger than 15 years were not included in the analysis concerning ICU scoring systems. To monitor FD to MR 17 (19%) the patients at the ICU, the APACHE II and the SOFA SC source (BM/PBSC/CB) 44/42/5 scores were used. The SOFA score assesses the function of SC dose ( Â 108/kg) 4.8 (0.2–25.8) CD34+ ( Â 106/kg) 6.6 (0.2–32.8) six different organ systems: respiratory (partial arterial oxygen pressure (PaO2)/fraction of inspired oxygen (FiO2)), GVHD prophylaxis cardiovascular (blood pressure, vasopressor use), renal No 1 (creatinine and diuresis), hepatic (bilirubin), neurological CsA+MTX 73 CsA+Pred 9 (Glasgow Coma Score) and hematological (platelet count). TcD 4 Normally, it was calculated once daily using the most Other combinations 4 abnormal data from the preceding 24 h and given a score from 0 (normal) to 4 (most abnormal) in each organ Conditioning system.19 SOFA and APACHE II scores were calculated TBI based 44 Chemotherapy 28 retrospectively for the first day at the ICU using the initial RIC 19 blood samples and patient clinical status at ICU arrival. ATG 63 (69%) Abbreviations: ATG ¼ antithymocyte globulin; CB ¼ cord blood; F ¼ female; ICU treatment FD to MR ¼ female donor to male recipient; HLA-id ¼ HLA-identical; The ventilation used at the ICU was distributed in three M ¼ male; MUD ¼ matched unrelated donor; Pred ¼ prednisolon; groups. All patients with spontaneous breathing, only RIC ¼ reduced-intensity conditioning; SC ¼ stem cell; TcD ¼ T-cell depletion. needing extra oxygen, were classified as spontaneous breathing. In the group with NIV, the most common and 31 December 2005. Of them, 91 patients (14%) were ventilation mode was continuous positive airway pressure admitted to the ICU during this period, and 4 patients were (CPAP) with assisted spontaneous breathing (CPAP-ASB). transferred to the ICU twice. The diagnoses for patients In the beginning of the studied period, pure CPAP without admitted to the ICU were hematological malignancies pressure assist was used. In the past years, CPAP was (n ¼ 65), solid tumors (n ¼ 7) and non-malignant diseases replaced by CPAP-ASB in our ICU. The third group, (n ¼ 9). Twenty-six patients (29%) were younger than 18 invasive ventilation, was defined by an intubation. In the years of age at the time of ASCT. Patient and donor beginning of the 11-year period studied, the dominating characteristics are shown in Table 1. ventilation mode was continuous positive pressure ventila- tion, which has been replaced by more lung-protective ventilation strategies such as BiPAB and CPAP-ASB. Conditioning The ventilation strategies with lower tidal volumes as A majority of patients received myeloablative conditioning recommended in the study from the ARDS network were (n ¼ 72). The myeloablative conditioning regimens con- implemented.5 A few patients received airway pressure sisted of CY (60 mg/kg daily) for 2 days in combination release ventilation (APRV). with either 10 Gy single-dose TBI or 12 Gy (4 Â 3 Gy) of As vasopressor/inotropy, norepinephrine was used alone fractionated TBI, or BU (4 mg/kg per day, divided in or in combination with epinephrine. Circulatory monitor- 4 doses). Nineteen patients received RIC.14 Sixty-three ing was performed with measurement of the arterial blood patients (69%) were treated with antithymocyte globulin pressure and central venous pressure. In the past years, (ATG) Thymoglobulin; Genzyme, Cambridge, MN, USA), transthoracic echocardiography was used to judge the for 3–5 days at a total dose of 4–8 mg/kg.15 cardiac output and volume status. Bone Marrow Transplantation SOFA predicts outcome of ICU care after SCT K Gilli et al 684 Fluid and volume substitution was initially performed by patients received antibiotics at admission or after admission albumin (4 and 20%); in the past years, albumin was to the ICU (Table 3). A majority of patients were also replaced by synthetic colloids such as hydroxyethylstarch. treated with antifungal and antiviral drugs. During ICU As crystalloid administration, Ringeracetat was used. treatment, the majority of patients were transfusion If needed, continuous venovenous hemodiafiltration dependent as shown in Table 3.
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