Tan H K, Lim J S S, Tan C K, Ng H S, Chow P, Lui H F, Wong G C, Tan P H C, Raghuram J, Ng H N, Choong L H L, Wong K S, Woo K T
Department of Renal Medicine, Singapore General Hospital, Singapore.
Liver Int. 2003;23 Suppl 3:52-60. doi: 10.1034/j.1478-3231.23.s.3.3.x.
BACKGROUND/METHODS: Molecular Adsorbent Recirculating System (MARS) was used in three consecutive critically ill patients at the Singapore General Hospital with advanced malignancy and acute liver failure (ALF). Case 1 was a male patient with hepatocellular carcinoma (HCC) for which initial right hepatectomy was followed by left hepatectomy 5 months later for recurrent HCC. The postoperative course following second surgery was complicated by severe methicillin-resistant Staphylococcus aureus (MRSA) sepsis, mild azotaemia and subacute cholestatic liver failure. MARS was used thrice in this patient. Case 2 was a female patient with advanced acute lymphoblastic leukaemia (ALL) with post bone marrow transplantation (BMT) acute haemolytic-uraemic syndrome (HUS) secondary to cyclosporin A (Cy A), cytomegalovirus (CMV) infection, severe nosocomial pneumonia, acute renal failure (ARF) treated with continuous haemofiltration and acute veno-occlusive disease resulting in Budd-Chiari syndrome. The latter precipitated ALF. MARS was instituted twice. Case 3 was a male patient with advanced, refractory Hodgkin's disease previously treated with multiple courses of chemotherapy. ALF developed secondary to acute viral hepatitis B flare. He was given a trial of MARS once in the ICU. All the three patients eventually died.
Mean MARS intradialytic systemic pressures were as follows: systolic pressure range was 95 +/- 17 to 128 +/- 17 mmHg and diastolic pressure range was 51 +/- 5 to 67 +/- 7 mmHg. Pressure at albumin dialysate exit point from dialyser 1 (Ae) ranged from 253 +/- 11 to 339 +/- 15 mmHg and that at albumin dialysate entry point into dialyser 1 (Aa) ranged from 142 +/- 11 to 210 +/- 6 mmHg. Ultrafiltration (UF) was 633 +/- 622 mL over mean treatment duration of 6.3 +/- 0.9 h with a total heparin dose of 1583 +/- 817 IU. Coagulation status pre- and 6-h post-MARS was similar: aPTT (P=0.116) and platelet count (P=0.753). There were no bleeding complications or circuit thromboses. MARS had a significant de-uraemization effect (pre- and post-MARS serum creatinine and urea: P=0.046 and 0.028, respectively) but did not significantly attenuate blood lactate, ammonia or total bilirubin levels. Albumin dialysate (Ae - Aa) urea and creatinine concentrations appeared to be sharply attenuated after 6 h of MARS. In contrast, the removal of total bilirubin by albumin dialysate from the blood compartment appeared to plateau after 4 h of continuous MARS operation.
MARS was well-tolerated in critically ill patients with advanced and complicated cancer. Low-dose heparin was safe and did not compromise MARS circuit integrity. Although MARS had a significant de-uraemization effect, this appeared to be limited by the duration of MARS operation. Our data suggested that such a limit was reached earlier for total bilirubin. More data are needed to confirm the present findings and further delineate the saturation limit of MARS for different toxins that accumulate in ALF. This would affect the optimal duration of MARS therapy.
背景/方法:新加坡总医院对3例患有晚期恶性肿瘤和急性肝衰竭(ALF)的重症患者连续使用分子吸附循环系统(MARS)。病例1是一名男性肝细胞癌(HCC)患者,最初行右肝切除术,5个月后因复发性HCC行左肝切除术。第二次手术后的病程并发严重耐甲氧西林金黄色葡萄球菌(MRSA)败血症、轻度氮质血症和亚急性胆汁淤积性肝衰竭。该患者使用MARS 3次。病例2是一名患有晚期急性淋巴细胞白血病(ALL)的女性患者,骨髓移植(BMT)后出现环孢素A(Cy A)继发的急性溶血尿毒综合征(HUS)、巨细胞病毒(CMV)感染、严重医院获得性肺炎、经持续血液滤过治疗的急性肾衰竭(ARF)以及导致布加综合征的急性肝静脉闭塞病。后者引发了ALF。使用MARS 2次。病例3是一名患有晚期难治性霍奇金病的男性患者,此前接受过多个疗程的化疗。ALF继发于急性乙型病毒性肝炎发作。在重症监护病房(ICU)对其试用MARS 1次。所有3例患者最终均死亡。
MARS透析期间的平均体循环压力如下:收缩压范围为95±17至128±17 mmHg,舒张压范围为51±5至67±7 mmHg。透析器1白蛋白透析液出口点(Ae)的压力范围为253±11至339±15 mmHg,而透析器1白蛋白透析液入口点(Aa)的压力范围为142±11至210±6 mmHg。在平均治疗时长6.3±0.9小时内超滤量(UF)为633±622 mL,肝素总剂量为1583±817 IU。MARS治疗前及治疗6小时后的凝血状态相似:活化部分凝血活酶时间(aPTT,P = 0.116)和血小板计数(P = 0.753)。未出现出血并发症或体外循环血栓形成。MARS具有显著的降尿素氮作用(MARS治疗前后血清肌酐和尿素:P分别为0.046和0.028),但未显著降低血乳酸、氨或总胆红素水平。MARS治疗6小时后,白蛋白透析液(Ae - Aa)中的尿素和肌酐浓度似乎急剧下降。相比之下,持续MARS运行4小时后,白蛋白透析液从血液中清除总胆红素的量似乎趋于平稳。
MARS在患有晚期复杂癌症的重症患者中耐受性良好。低剂量肝素安全且不影响MARS体外循环的完整性。尽管MARS具有显著的降尿素氮作用,但这似乎受MARS运行时长的限制。我们的数据表明,总胆红素更早达到这样的极限。需要更多数据来证实目前的发现,并进一步明确MARS对ALF中蓄积的不同毒素的饱和极限。这将影响MARS治疗的最佳时长。