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

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 preand-post-dilution to those by post-dilution only.

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

Multiple organ failure is the disease

with severely progression and makes many

patients stayed at intensive care unit

(ICU) for a long time Although therapeutic

progresses, the mortality rates remained

the highest in ICU So that, besides of the

intensive treatment methods, the supportive

assistance is always focused to improve

organ function and reduce mortality rates

CRRT can replace the decreased kidney

function and release inflammatory cytokines This technique was supported for patients with MOF in many researchers, but there have not had any trials comparing pre-and-post-dilution CRRT with post-dilution one Therefore, this study is for objectives:

Evaluating the outcome of the MOF patients supported by pre-and-post-dilution CRRT and comparing some factors related to the results, progression and prognosis of the patients supported by pre-and-post-dilution to those by post-pre-and-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

SUBJECTS AND METHODS

1 Subjects

77 patients with MOF appointed for

CRRT, including 2 groups: 41 patients in

group 1 (study group) supported by

pre-and-post-dilution and 36 patients in group

2 (control group) supported by post-dilution,

were treated at ICU of People's Hospital

115 from Feb 2014 to Feb 2016

* The inclusion criteria:

- Patient age > 18 years diagnosed of

MOF according to the SOFA score (table 1)

+ 6 organs: Cardiovascular, respiratory,

kidney, liver, coagulation, CNS

+ Criteria: SOFA score ≥ 2 and total

SOFA score increase at least 1 point

compared with admission

+ Acute liver failure (ALF) with 1 in 2

following criteria: Total bilirubin level

> 1.9 mg/dL or having all of 3 criteria of

ALF by the AASLD (table 3)

+ MOF: At least 2 failured organs and

lasting more than 24 hours

- Having the acute kidney injury identified

by RIFLE criteria (table 2): Serum creatinine

increased 2 times baseline or urine output

< 0.5 mL/kg/h x 12h

- Causes of MOF were different: sepsis,

shock, acute pancreatitis

- With or without identified chronic

diseases

- Receiving continuous veno-venous

hemofiltration (CVVH)

* The exclusion criteria:

- MOF without AKI

- Died within 24 hours after admission

to ICU

- Lack of test of kidney function after intervention

- Indicated for surgery without effective treatment

- The end-stage disease: decompensated cirrhosis, metastatic cancer…

- Pregnant or breastfeeding

2 Methods

* Trial design: Prospective, compare

before and after intervention

* Trial content:

- Doing clinical examination and test for evaluating organ injury, consists of urea, creatinine, bilirubine, platelet, IL-6, TNF- , arterial blood gas (pH, PaCO2, HCO3-, aO2, PaO2/FiO2)

- Critical care and treating basic diseases

- Setting CRRT for two groups with the parameters such as mode: continuous veno-venous hemofiltration; input: femoral vein or internal jugular vein; filter: AN69, if being clotted, change the new; heparin dose: 500 - 1,000 UI/h; blood flow: 120 -

150 mL/mn, replacement flow: 30 -

40 mL/kg/h; output flow: 0 - 200 mL/h, it was depended on body fluid through by charateristics as edema, weight, CVP, urine output, blood pressure; dilution:

group 1 (pre-and-post-dilution), group 2 (post-dilution)

- Criteria for stopping CRRT: Recovering shock: heart rate < 110 bpm, MAP

≥ 70 mmHg, CVP < 12 cmH2O, blood pressure is still stable after stopping vasopressors ≥ 2h, UO > 50 mL/h, serum creatinin < 1.6 mg/dL Patient is died or too heavy to cure

- Doing blood test: after 12h (T12), 24h (T24), 48h (T48), end of CRRT (Tn)

* Criteria for diagnosis, classification in the study:

Table 1: SOFA score

Respiratory

Cardiovascular

Dopamin ≤ 5 or dobutamin (any dose)

Dopamin > 5 or epinephrine ≤ 0,1

or NE ≤ 0,1

Dopamin > 15 or epinephrine > 0,1

or NE > 0,1 Kidney

creatinine (mg/dL)

or urine output (mL/day)

< 500

> 5

< 200 Liver

Coagulation

Central nervous system

(*: Adrenergic agents administered for at least one hour [[doses given are in µg/kg/min]) Table 2: RIFLE criteria

Failure

Increased creatinine x 3

or creatinine ≥ 4 mg/dL

(acute rise of ≥ 0,5 mg/dL)

UO < 0.5 mL/kg/h x 24h

or anuria x 12h

Table 3: Definition of acute liver failure by the AASLD (American Association for the

Study of Liver Diseases)

Grade 1: Changes in behavior with minimal change in

level of consciousness Grade 2: Gross disorientation, drowsiness, possibly

asterixis, inappropriate behavior Grade 3: Marked confusion, incoherent speech, sleeping most of the time but arousable to vocal stimuli Encephalopathy

Grade 4: Comatose, unresponsive to pain, decorticate or decerebrate posturing

* Data analysis: Using SPSS 22 to analyse the percentage and the average values

RESULTS

1 The common characteristics of patients

Table 4: Compare some common characteristics between the 2 groups

Type of injured organ

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

The percentage and average values of clinical and subclinical parameters between the 2 groups were similar

2 Compare some results between the two groups

Table 6: Compare serum ure and creatinin between the 2 groups

Parameters

p

Urea (mg/dL)

Creatinine (mg/dL)

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

IL-6 (pg/mL)

TNF-α (pg/mL)

- 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

Table 8: Number of injured organ at the Tn

Injured

- 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

- 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

Coma at hospitalization

Mechanical ventilation

APACHE II score ≥ 25

SOFA score (at day 1) > 10

Failure > 3 organs

The factors as coma at hospitalization, mechanical ventilation, APACHE II score ≥ 25, SOFA score > 10, failure > 3 organs increased patients' mortality

DISCUSSION

77 patients in this trial were treated

MOF with guidelines and recommendations

They also were supported by CRRT

with two dilution modes The common

characteristics, clinical and subclinical

parameters were similar in the two

groups This similarity was the basis for

evaluating and comparing the effect of

pre-and-dilution CRRT with

post-dilution CRRT in MOF patients

Continuous renal replacement therapy

is one of mainly kidney replacement

methods in treating AKI with oliguria/

anuria In this study, serum urea and

creatinine decreased gradually after CRRT

and there was the difference between the

two groups before intervention; as well as

at 12h, and 24h after intervention But at

the end of CRRT, the average value of

serum urea and creatinine in group used

pre-and-post-dilution was statistically lower

than that in group used post-dilution

2 multicenter randomized studies - RENAL

and ATN showed that the effect of CRRT

in improving kidney function in severe

patients with AKI 4, 5]

About the inflammatory cytokine clearance, study showed that concentrations of serum IL-6 and TNF-α decreased after CRRT and there had not difference between the two groups Especially, while analyzing

by paired-samples t-test, results showed that CRRT could purify the inflammatory cytokines clearly IL-6 concentrations were significantly reduced in both groups, while TNF-α levels were only statistically significantly reduced in group 1 Hoang Van Quang and Nguyen Gia Binh also recorded CRRT reduced the concentrations

of cytokines [1, 2] However, Cole and Klouche proved that although improved prognosis, CRRT did not change blood cytokine level, this was explained to be related to "immune threshold hypothesis",

in which the removing cytokines from the blood leads to removing cytokines in the tissue due to the balance of concentration [6]

At the end of study, the mean number

of injured organ in the two groups was not different However, when comparing each group of organ failure, the impairment of

≤ 3 organs did not differ between the two

groups, the group 1 had more patients

with 4 organs failure whereas ≥ 5 organs

had significantly less compared with

group 2 It means that the tendency of

severe progression in study group was

less than that of control group Besides,

study also recorded the average filter

lifetime with pre-and-post-dilution was

significantly longer than that with

post-dilution (31.9 ± 10.8 hours versus 26.7 ±

10.6 hours) Van der Voort and Uchino

showed that post-dilution shortened the

filter lifetime compared with pre-dilution

[7, 8]

Multiple organ failure is the disease

with severely progression and influences

many organs Results of the study

showed that, the factors as coma at

hospitalization, mechanical ventilation,

APACHE II score ≥ 25, SOFA score > 10,

failure of > 3 organs increased patients'

mortality Study of Nguyen Gia Binh

recorded APACHE II score > 25 và

impairment of > 3 organs was related to

mortality [2] Hoang Van Quang also said

that APACHE II, SOFA and failure more

organs were related to prognosis [1]

Truong Ngoc Hai researched and

identified the factors related to mortality,

and concluded that age ≥ 55, mechanical

ventilation, pH < 7.1; APACHE II score

≥ 25, SOFA score ≥ 10 and failure of

> 3 organs were the prognosis factors [3]

CONCLUSIONS

Studying MOF patients supported by

pre-and-post-dilution CRRT and comparing

with those supported by post-dilution, had

the folowing results:

* Common results:

- At the end of CRRT, serum urea and creatinine as well as percentage of AKI in group used pre-and-post-dilution were

lower than that in control group

- At the end of CRRT, percentage of injury ≥ 5 organs was lower

- The variability of IL-6, TNF-α and parameters of arterial blood gas had not the statistically difference between the

2 groups

* Some factors related to the results, progression and prognosis:

- Average filter lifetime was longer while

using pre-and-post-dilution CRRT

- Mechanical ventilation time, days in ICU and mortality were not statistically

significant between the 2 groups

- The factors ascoma at hospitalization, mechanical ventilation, APACHE II score

≥ 25, SOFA score > 10, failure > 3 organs increased patients' mortality

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