Results of treatment of patients with multiple organ failure supported by pre - and post - dilution continuous renal replacement therapy

Nội dung text: Results of treatment of patients with multiple organ failure supported by pre - and post - dilution continuous renal replacement therapy

1. Journal of military pharmaco-medicine n o2-2018 RESULTS OF TREATMENT OF PATIENTS WITH MULTIPLE ORGAN FAILURE SUPPORTED BY PRE-AND POST-DILUTION CONTINUOUS RENAL REPLACEMENT THERAPY Huynh Thi Ngoc Thuy*; Hoang Trung Vinh**; Do Quoc Huy* SUMMARY Objectives: To evaluate the outcome of the patients with multiple organ failure (MOF) supported by pre-and-post-dilution continuous renal replacement therapy (CRRT) and compare some factors related to the results, progression and prognosis of the patients supported by pre- and-post-dilution to those by post-dilution only. Subjects and methods: Prospective trial, compared before and after intervention in 77 patients diagnosed of MOF according to SOFA score, including 2 groups: 41 patients in group 1 (study group) (supported by pre-and-post- dilution), 36 patients in group 2 (control group) (supported by post-dilution). Data were received from clinical examination, diagnostic tests during treatment. Results: Comparing with post- dilution, patients in group of pre-and-post-dilution had lower serum creatinine at the end of study (1.6 ± 0.9 mg/dL versus 2.3 ± 1.5 mg/dL), higher TNF-α clearance (16.8 pg/mL versus 4.0 pg/mL), filter lifetime was longer (31.9 ± 10.8 h versus 26.7 ± 10.6 h), the percentage of patients with acute kidney injury (AKI) as well as failure of ≥ 5 were lower at the end of the study (36.6% vs 72.2% and 24.4% vs 50%). The mortality rates of the two groups were similar (70.7% and 72.2%). Conclusion: Pre-and-post-dilution has many advantages in improving kidney function, purifying cytokines and prolonging the filter lifetime. * Keywords: Multiple organ failure; Continuous renal replacement therapy; Post-dilution; Pre- and-post-dilution. INTRODUCTION function and release inflammatory cytokines. This technique was supported for patients Multiple organ failure is the disease with MOF in many researchers, but there with severely progression and makes many have not had any trials comparing pre- patients stayed at intensive care unit and-post-dilution CRRT with post-dilution (ICU) for a long time. Although therapeutic one. Therefore, this study is for objectives: progresses, the mortality rates remained Evaluating the outcome of the MOF patients the highest in ICU. So that, besides of the supported by pre-and-post-dilution CRRT intensive treatment methods, the supportive and comparing some factors related to assistance is always focused to improve the results, progression and prognosis of organ function and reduce mortality rates. the patients supported by pre-and-post- CRRT can replace the decreased kidney dilution to those by post-dilution only. ** People’s Hospital 115 *** 103 Military Hospital Corresponding author: Huynh Thi Ngoc Thuy (bshuynhngocthuy@gmail.com) Date received: 21/11/2017 Date accepted: 18/01/2018 113 113
2. Journal of military pharmaco-medicine n o2-2018 SUBJECTS AND METHODS - Lack of test of kidney function after intervention. 1. Subjects. - Indicated for surgery without effective 77 patients with MOF appointed for treatment. CRRT, including 2 groups: 41 patients in - The end-stage disease: decompensated group 1 (study group) supported by pre- cirrhosis, metastatic cancer and-post-dilution and 36 patients in group 2 (control group) supported by post-dilution, - Pregnant or breastfeeding. were treated at ICU of People's Hospital 2. Methods. 115 from Feb 2014 to Feb 2016. * Trial design: Prospective, compare * The inclusion criteria: before and after intervention. - Patient age > 18 years diagnosed of * Trial content: MOF according to the SOFA score ( table 1 ). - Doing clinical examination and test + 6 organs: Cardiovascular, respiratory, for evaluating organ injury, consists of kidney, liver, coagulation, CNS. urea, creatinine, bilirubine, platelet, IL-6, TNF- , arterial blood gas (pH, PaCO , + Criteria: SOFA score ≥ 2 and total 2 HCO -, aO , PaO /FiO ). SOFA score increase at least 1 point 3 2 2 2 compared with admission. - Critical care and treating basic diseases. + Acute liver failure (ALF) with 1 in 2 - Setting CRRT for two groups with the following criteria: Total bilirubin level parameters such as mode: continuous > 1.9 mg/dL or having all of 3 criteria of veno-venous hemofiltration; input: femoral vein or internal jugular vein; filter: AN69, if ALF by the AASLD ( table 3 ). being clotted, change the new; heparin + MOF: At least 2 failured organs and dose: 500 - 1,000 UI/h; blood flow: 120 - lasting more than 24 hours. 150 mL/mn, replacement flow: 30 - - Having the acute kidney injury identified 40 mL/kg/h; output flow: 0 - 200 mL/h, it by RIFLE criteria ( table 2 ): Serum creatinine was depended on body fluid through by increased 2 times baseline or urine output charateristics as edema, weight, CVP, < 0.5 mL/kg/h x 12h. urine output, blood pressure; dilution: - Causes of MOF were different: sepsis, group 1 (pre-and-post-dilution), group 2 shock, acute pancreatitis. (post-dilution). - With or without identified chronic - Criteria for stopping CRRT: Recovering diseases. shock: heart rate < 110 bpm, MAP ≥ 70 mmHg, CVP < 12 cmH O, blood - Receiving continuous veno-venous 2 pressure is still stable after stopping hemofiltration (CVVH). vasopressors ≥ 2h, UO > 50 mL/h, serum * The exclusion criteria: creatinin < 1.6 mg/dL. Patient is died or - MOF without AKI. too heavy to cure. - Died within 24 hours after admission - Doing blood test: after 12h (T12), 24h to ICU. (T24), 48h (T48), end of CRRT (Tn). 114
3. Journal of military pharmaco-medicine n o2-2018 * Criteria for diagnosis, classification in the study: Table 1: SOFA score. SOFA score 1 2 3 4 Respiratory ≤ 200 with ≤ 100 with ≤ 400 ≤ 300 PaO 2/FiO 2 (mmHg) respiratory support respiratory support Dopamin ≤ 5 or Dopamin > 5 or Dopamin > 15 or Cardiovascular MAP 0,1 hypotension* (any dose) or NE ≤ 0,1 or NE > 0,1 Kidney 3,5 - 4,9 > 5 creatinine (mg/dL) 1,2 - 1,9 2 - 3,4 < 500 < 200 or urine output (mL/day) Liver 1,2 - 1,9 2 - 5,9 6 - 11,9 > 12 total bilirubine (mg/dL) Coagulation 3 3 ≤ 150 ≤ 100 ≤ 50 ≤ 20 platelets x 10 /mm Central nervous system 13 - 14 10 -12 6 - 9 < 6 Glasgow coma score (*: Adrenergic agents administered for at least one hour [[doses given are in µg/kg/min]) Table 2: RIFLE criteria. Creatinine criteria Urine output criteria Risk Increased creatinine x 1,5 UO < 0.5 mL/kg/h x 6h Injury Increased creatinine x 2 UO < 0.5 mL/kg/h x 12h Increased creatinine x 3 UO < 0.5 mL/kg/h x 24h Failure or creatinine ≥ 4 mg/dL or anuria x 12h (acute rise of ≥ 0,5 mg/dL) Loss Persistent ARF = complete loss of renal function > 4 weeks ESRD End stage renal disease Table 3: Definition of acute liver failure by the AASLD (American Association for the Study of Liver Diseases). Criteria Characteristics Acute liver disease < 26 weeks without preexisting cirrhosis Grade 1: Changes in behavior with minimal change in level of consciousness Grade 2: Gross disorientation, drowsiness, possibly Encephalopathy asterixis, inappropriate behavior Grade 3: Marked confusion, incoherent speech, sleeping most of the time but arousable to vocal stimuli Grade 4: Comatose, unresponsive to pain, decorticate or decerebrate posturing Coagulation abnormality INR ≥ 1,5 * Data analysis: Using SPSS 22 to analyse the percentage and the average values. 115
4. Journal of military pharmaco-medicine n o2-2018 RESULTS 1. The common characteristics of patients. Table 4: Compare some common characteristics between the 2 groups. Parameters Group 1 (n = 41) Group 2 (n = 36) p Average age (year) 66.00 ± 16.17 68.28 ± 18.54 > 0.05 Female (n, %) 24 (53,3%) 21 (46.7%) > 0.05 Male (n, %) 17 (53.1%) 15 (46.9%) Chronic disease (n, %) 28 (58.3%) 20 (41.7%) > 0.05 Number of injured organ 3.8 ± 0.9 3.8 ± 1 > 0.05 Type of injured organ Kidney (n, %) 41 (100%) 36 (100%) Cardiovascular system (n, %) 38 (92.7%) 32 (88.9%) > 0.05 Lung (n, %) 35 (85.4%) 30 (83.3%) > 0.05 Central neutral system (n, %) 22 (53.7%) 23 (63.9%) > 0.05 Coagulation (n, %) 14 (34.1%) 11 (30.6%) > 0.05 Liver (n, %) 9 (22%) 8 (22.2%) > 0.05 Age, sex, chronic disease, number and type of injured organs were not different between the 2 groups. Table 5: Compare some clinical and subclinical characteristics. Parameters Group 1 (n = 41) Group 2 (n = 36) p MAP 0.05 Ventilation (n, %) 34 (54%) 29 (46%) > 0.05 Oliguria/anuria (n, %) 29 (70.7%) 23 (63.9%) > 0.05 Creatinine (mg/dL) 3.3 ± 2.3 3.7 ± 2.1 > 0.05 Total bilirubine (mg/dL) 2.3 ± 2.4 5.7 ± 6.6 > 0.05 Platelet (K/µL) 192.9 ± 131.9 155.1 ± 78.1 > 0.05 IL-6 (pg/mL) 2,310.7 ± 2,178.2 1,429.7 ± 1,626.1 > 0.05 TNF-α (pg/mL) 49.0 ± 41.9 45.3 ± 41.7 > 0.05 pH 7.21 ± 0.10 7.24 ± 0.16 > 0.05 PaCO 2 (mmHg) 39.9 ± 15.5 40.2 ± 27.7 > 0.05 - HCO 3 (mmol/L) 16.3 ± 5.6 16.6 ± 6.7 > 0.05 PaO 2 (mmHg) 97.6 ± 62.3 102.8 ± 92.3 > 0.05 PaO 2/FiO 2 222.1 ± 142.4 243.7 ± 239.1 > 0.05 The percentage and average values of clinical and subclinical parameters between the 2 groups were similar. 116
5. Journal of military pharmaco-medicine n o2-2018 2. Compare some results between the two groups. Table 6: Compare serum ure and creatinin between the 2 groups. Group 1 (n = 41) Group 2 (n = 36) Parameters p Number X ± SD Number X ± SD Urea (mg/dL) T0 41 96.7 ± 55.8 36 144.8 ± 90.0 > 0.05 T12 41 78.8 ± 44.5 36 94.0 ± 62.9 > 0.05 T24 41 56.1 ± 29.9 36 75.9 ± 41.9 > 0.05 Tn 41 68.9 ± 39.8 36 98.3 ± 52.3 < 0.01 Creatinine (mg/dL) T0 41 3.4 ± 2.3 36 3.7 ± 2.1 > 0.05 T12 41 2.6 ± 1.7 36 2.5 ± 1.8 > 0.05 T24 41 1.9 ± 1.3 36 2.0 ± 1.2 > 0.05 Tn 41 1.6 ± 0.9 36 2.3 ± 1.5 < 0.05 The average values of serum urea and creatinine in group 1 was statistically lower than that in group 2 at the end of study. Table 7: Compare serum IL-6 và TNF-α between the 2 groups. Group 1 (n = 41) Group 2 (n = 36) p Number X ± SD Number X ± SD IL-6 (pg/mL) Before CRRT 40 2,310.7 ± 2,178.2 34 1,429.8 ± 1,626.1 > 0.05 After CRRT 40 966.0 ± 1,444.3 34 791.2 ± 1,478.3 > 0.05 ∆ after-before 40 (-) 1,344.7 ± 1,720.1 34 (-) 638.5 ± 1,723.6 > 0.05 p∆ < 0.001 < 0.05 TNF-α (pg/mL) Before CRRT 23 49.0 ± 41.9 22 45.3 ± 41.7 > 0.05 After CRRT 23 32.2 ± 14.4 22 41.3 ± 19.9 > 0.05 ∆ after-before 23 (-) 16.8 ± 31.7 22 (-) 4.0 ± 39.2 > 0.05 p∆ 0.05 - IL-6 concentrations were significantly reduced in both groups. - TNF-α level was only statistically significantly reduced in group 1. - Before and after intervention, the variability of serum IL-6 and TNF-α was not different between the 2 groups. 117
6. Journal of military pharmaco-medicine n o2-2018 Table 8: Number of injured organ at the Tn. Injured Group 1 (n = 41) Group 2 (n = 36) p organs Number (n) Percentage (%) Number (n) Percentage (%) 0 6 14.6 2 5.6 > 0.05 1 3 7.3 6 16.7 > 0.05 2 3 7.3 2 5.6 > 0.05 3 4 9.8 3 8.3 > 0.05 4 16 39 5 13.8 < 0.05 ≥ 5 9 22 18 50 < 0.05 - At the end of CRRT, the patients with failure of 4 organs in group 1 were higher whereas those of ≥ 5 organs were significantly less than group 2. - The percentage of 2 - 3 failure organs or without was similar in the 2 groups. Table 9: Some factors related to the results and mortality of the 2 groups. Parameters Group 1 (n = 41) Group 2 (n = 36) p Average filter lifetime (hour) 31.9 ± 10.8 26.7 ± 10.6 < 0.05 Replacement volume (mL/kg/h) 36.4 ± 4.1 37.9 ± 5.6 > 0.05 Mechanical ventilation (days) 5.4 ± 5.1 8.9 ± 10.2 > 0.05 Days in ICU 7.7 ± 5.9 9.9 ± 10.4 > 0.05 Mortality (n, %) 29 (70.7%) 26 (72.2%) > 0.05 - Average filter lifetime in group1 was longer than that in group 2. - The other parameters were similar in the 2 groups. Table 10: Estimated mortality of some factors. Survey factors n (%) Odd ratio (OR) 95%CI p Coma at hospitalization Died 15 (93.8%) 7.87 0.97 - 63.79 < 0.05 Survived 1 (6.2%) Mechanical ventilation Died 45 (80.4%) 4.50 1.53 - 13.26 < 0.01 Survived 11 (19.6%) APACHE II score ≥ 25 Died 45 (78.9%) 3.75 1.27 - 11.08 < 0.05 Survived 12 (21.1%) 118
7. Journal of military pharmaco-medicine n o2-2018 SOFA score (at day 1) > 10 Died 44 (83%) 5,78 1.97 - 16.95 < 0.01 Survived 9 (17%) Failure > 3 organs Died 39 (81.3%) 3,52 1,26 - 9,86 < 0,05 Survived 9 (18.7%) The factors as coma at hospitalization, mechanical ventilation, APACHE II score ≥ 25, SOFA score > 10, failure > 3 organs increased patients' mortality. DISCUSSION About the inflammatory cytokine clearance, 77 patients in this trial were treated study showed that concentrations of serum MOF with guidelines and recommendations. IL-6 and TNF-α decreased after CRRT They also were supported by CRRT and there had not difference between the with two dilution modes. The common two groups. Especially, while analyzing characteristics, clinical and subclinical by paired-samples t-test, results showed parameters were similar in the two that CRRT could purify the inflammatory groups. This similarity was the basis for cytokines clearly. IL-6 concentrations evaluating and comparing the effect of were significantly reduced in both groups, pre-and-post-dilution CRRT with post- while TNF-α levels were only statistically dilution CRRT in MOF patients. significantly reduced in group 1. Hoang Continuous renal replacement therapy Van Quang and Nguyen Gia Binh also is one of mainly kidney replacement recorded CRRT reduced the concentrations methods in treating AKI with oliguria/ of cytokines [1, 2]. However, Cole and anuria. In this study, serum urea and Klouche proved that although improved creatinine decreased gradually after CRRT prognosis, CRRT did not change blood and there was the difference between the cytokine level, this was explained to be two groups before intervention; as well as related to "immune threshold hypothesis", at 12h, and 24h after intervention. But at in which the removing cytokines from the the end of CRRT, the average value of blood leads to removing cytokines in the serum urea and creatinine in group used tissue due to the balance of concentration pre-and-post-dilution was statistically lower [6]. than that in group used post-dilution. At the end of study, the mean number 2 multicenter randomized studies - RENAL of injured organ in the two groups was not and ATN showed that the effect of CRRT different. However, when comparing each in improving kidney function in severe group of organ failure, the impairment of patients with AKI 4, 5]. ≤ 3 organs did not differ between the two 119
8. Journal of military pharmaco-medicine n o2-2018 groups, the group 1 had more patients * Common results: with 4 organs failure whereas ≥ 5 organs - At the end of CRRT, serum urea and had significantly less compared with creatinine as well as percentage of AKI in group 2. It means that the tendency of group used pre-and-post-dilution were severe progression in study group was lower than that in control group. less than that of control group. Besides, - At the end of CRRT, percentage of study also recorded the average filter injury ≥ 5 organs was lower. lifetime with pre-and-post-dilution was - The variability of IL-6, TNF-α and significantly longer than that with post- parameters of arterial blood gas had not dilution (31.9 ± 10.8 hours versus 26.7 ± the statistically difference between the 10.6 hours). Van der Voort and Uchino 2 groups. showed that post-dilution shortened the filter lifetime compared with pre-dilution * Some factors related to the results, [7, 8]. progression and prognosis: Multiple organ failure is the disease - Average filter lifetime was longer while with severely progression and influences using pre-and-post-dilution CRRT. many organs. Results of the study - Mechanical ventilation time, days in showed that, the factors as coma at ICU and mortality were not statistically hospitalization, mechanical ventilation, significant between the 2 groups. APACHE II score ≥ 25, SOFA score > 10, - The factors ascoma at hospitalization, failure of > 3 organs increased patients' mechanical ventilation, APACHE II score mortality. Study of Nguyen Gia Binh ≥ 25, SOFA score > 10, failure > 3 organs recorded APACHE II score > 25 và increased patients' mortality. impairment of > 3 organs was related to mortality [2]. Hoang Van Quang also said REFERENCES that APACHE II, SOFA and failure more 1. Hoàng V ăn Quang. Nghiên c ứu đặ c organs were related to prognosis [1]. điểm lâm sàng và k ết qu ả điều tr ị suy đa t ạng Truong Ngoc Hai researched and ở b ệnh nhân s ốc nhi ễm khu ẩn. Lu ận án Ti ến sỹ Y h ọc. Tr ường Đạ i h ọc Y Hà N ội. 2009. identified the factors related to mortality, and concluded that age ≥ 55, mechanical 2. Nguy ễn Gia Bình, Đặng Qu ốc Tu ấn, Đỗ Tất C ường, Tr ần Duy Anh, Đỗ Qu ốc Huy và ventilation, pH < 7.1; APACHE II score CS. Nghiên c ứu ứng d ụng m ột s ố k ỹ thu ật l ọc ≥ 25, SOFA score ≥ 10 and failure of máu hi ện đạ i trong c ấp c ứu, điều tr ị m ột s ố > 3 organs were the prognosis factors [3]. bệnh. Đề tài c ấp Nhà n ước. B ộ Khoa h ọc và CONCLUSIONS Công ngh ệ - B ộ Y t ế. 2008. 3. Tr ươ ng Ng ọc H ải. Nghiên c ứu lâm Studying MOF patients supported by sàng, c ận lâm sàng và hi ệu qu ả điều tr ị c ủa pre-and-post-dilution CRRT and comparing li ệu pháp l ọc máu liên t ục ở b ệnh nhân suy with those supported by post-dilution, had đa t ạng. Lu ận án Ti ến s ỹ Y h ọc. H ọc vi ện the folowing results: Quân y. 2009. 120
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