Allocation of patients with liver cirrhosis and organ failure to intensive care: Systematic review and a proposal for clinical practice

Table 1 Included trials/studies

Author, year, location, study design	Main target of the study	Patient population	Scores	Allocation system	In hospital mortality	ICU mortality
Kavli et al[7], 2012, Denmark, cohort study	This study investigated the severity of organ failure, and the frequency and outcome of withholding therapy in patients with advanced alcoholic liver cirrhosis admitted to a Scandinavian ICU	87 adult patients with clinical or histological diagnosis of liver cirrhosis admitted to ICU at a University hospital in Denmark, within a 3 years period from January 2007-January 2010	APACHE II, SAPS II, and SOFA were better at predicting mortality than Child-Pugh score	No specific allocation system is proposed	Only ICU data	With 3 or more organ failures the ICU mortality was > 90%
Shawcross et al[1], 2012, United Kingdom, cohort study	The aim of this study was to prospectively study the resource allocation and cost of a large cohort of patients with cirrhosis and one or more extrahepatic organ failure(s)	563 patients were admitted to the Liver ICU at King’s College Hospital, between 2000 and 2007	The median (IQR) for all patients admitted and surviving for > 8 h on day 1 (n = 548) was Child-Pugh score 12 (11-13), MELD 25 (14-34), APACHE II 22 (16-28) and SOFA 11 (8-13)	No specific allocation system is proposed	Overall hospital mortality of 59% (330/563)	256/563 (51%) patients died whilst in the Liver ICU
				Patients with cirrhosis admitted to ICU require high levels of organ support but ICU admission is not necessarily futile
Ginès et al[9], 2012, Spain, review	This review focuses on the diagnostic approach and treatment strategies cur-rently recommended in the critical care management of patients with cirrhosis	None	MELD and Child-Pugh scores have important limitations in the establishment of prognosis in critically ill cirrhotic patients	Encephalopatic cirrhotic patients (grade 3 or 4 hepatic encephalopathy) require ICU admission and intubation	Hospital mortality rates in patients with 1, 2 or 3 organ/system failures were 48%, 65%, and 70%, respectively	ICU and 6-mo mortality rates of 41% and 62%, respectively
				Patients with a low MELD score (< 15), should be immediately considered for ICU. Contrary, in patients with end-stage cirrhosis (MELD > 30), 3 or more organ failures, and no perspective of transplantation, aggressive management is questionable		59% of cirrhotic patients placed on mechanical ventilation died during their stay in the ICU
Berry et al[10], 2013, United Kingdom, review	This review focuses on patients with cirrhosis, especially survival analysis and prognostic models		Child-Pugh score does not perform as well as general critical illness scoring systems	No specific allocation system is proposed	Greater than 60%	ICU mortality of up to 65%, rising to 90% with sepsis, if more than 1 d of respiratory support and renal support were required
			The MELD score performs better than the Child-Pugh score, yet the SOFA score is superior to both Child-Pugh and MELD score	Early aggressive approach to organ support is justified
Saliba et al[11], 2013, France, review	This review focuses on prognostic scores and admission to ICU for critically ill cirrhotic patients	None	Suggests that ICU scores (SOFA, APACHE II, SAPS II) predict the outcome of cirrhotic patients admitted to the ICU better than liver scores (MELD and Child-Pugh)	No specific allocation system is proposed	Only ICU data	Ranges between 34%-69%
				The persistence after ICU admission of three or more organ failures and the need for three or more organ supports, may lead to consider a limitation in life sustaining treatments, as a fatal outcome is almost constant

Included studies of the present review. The table describes the included studies. ICU: Intensive care unit; SOFA score: Sequential Organ Failure Assessment score; MELD: Model of End-stage Liver Disease.

Table 2 Scoring systems to predict mortality

Score	Target	Number of studies	AUCROC range(min-max)
Child-Pugh	Prognostic1	14	0.71-0.87
MELD	Prognostic1	8	0.77-0.93
RFH	Prognostic1	1	0.79
SOFA	Organ failure2	11	0.81-0.95
APACHE II	Prognostic in ICU3	9	0.66-0.83
APACHE III	Prognostic in ICU3	4	0.78-0.91

¹Prognostic: score used to assess the prognosis of chronic liver disease;

²Organ failure: score with the objective to evaluate the degree of organ failure;

³Prognostic in ICU: severity of disease classification score. The table describes the performance of the presented scoring systems[17,19-35]. AUROC: Areal Under the Reciever Operating Curve; Range (min-max) describing the minimum and maximum reported AUC for the given score, based on published trials[17,19-35]. ICU: Intensive care unit; MELD: Model of End-stage Liver Disease; RFH: Royal Free Hospital Score; SOFA: Sequential Organ Failure Assessment score; APACHE: Acute Physiology and Chronic Health Evaluation.

Table 3 Child-Pugh score

Measure	1 point	2 points	3 points
Total billirubin (μmol/L)	< 34 (< 1.9 mg/dL)	34-50 (< 1.9-2.9 mg/dL)	> 50 (> 2.9 mg/dL)
S-Albumin (g/L)	> 35	28-35	< 28
PT INR	< 1.70	1.71-2.30	> 2.30
Ascites	None	Mild	Moderate/severe
Hepatic encephalopathy	None	Grade I-II	Grade III-IV
Points	Class	One year survival	Two year survival
5-6	A	100%	85%
7-9	B	81%	57%
10-15	C	45%	35%

Child-Pugh Score and associated one- and two-year survival.

Table 4 World Health Organization performance score

Grade	WHO Performance score
0	Fully active, able to carry on all pre-disease performance without restriction
1	Restricted in physically strenuous activity but ambulatory and able to carry out work of a light or sedentary nature, e.g., light house work, office work
2	Ambulatory and capable of all selfcare but unable to carry out any work activities. Up and about more than 50% of waking hours
3	Capable of only limited selfcare, confined to bed or chair more than 50% of waking hours
4	Completely disabled. Cannot carry on any selfcare, totally confined to bed or chair
5	Dead

WHO: World Health Organization.

Table 5 Chronic Liver Failure-Sequential Organ Failure Assessment score

Organ	Variabel	0	1	2	3	4
Liver	Billirubin, μmol/L	< 20 μmol/L	≥ 20 to < 34 μmol/L	≥ 34 to < 103 μmol/L	≥ 103 to < 205 μmol/L	> 205 μmol/L
	(mg/dL)	(-1.1)	(≥ 1.1 to < 1.9 )	(≥ 1.9 to < 6.0)	(≥ 6.0 to < 11.9)	(> 11.9)1
Kidney	Creatinine, μmol/L	< 106 μmol/L	≥ 106 to < 177 μmol/L	≥ 177 to < 309 μmol/L	≥ 309 to < 442 μmol/L	> 442 μmol/L
	(mg/dL)	(< 1.2)	(≥ 1.2 to < 2.0)	(≥ 1.2 to < 3.5)1	(≥ 3.5 to < 5)1	(> 5.0)1
				Or renal replacement therapy1
CNS	HE grade	None	I	II	III1	IV1
Coagulation	INR	< 1.1	≥ 1.1 to 1.25	≥ 1.25 to < 1.5	≥ 1.5 to < 2.5	≥ 2.5 or platlets < 201
Circulation	MAP (mmHg)	≥ 70	< 70	Dopamine ≤ 51	Dopamine > 51	Dopamine > 15
				Dobutamine	Epinephrine ≤ 0.11	Epinephrine > 0.1
				Terlipressin1	Norepinephrine ≤ 0.11	Norepinephrine > 0.11
Lungs	PaO2/FiO2	> 400	> 300 to ≤ 400	> 200 to ≤ 300	> 100 to ≤ 2001	≤ 1001
	SpO2/FiO2	> 512	> 357 to ≤ 512	> 214 to < 357	> 89 to ≤ 2141	≤ 891

¹Indicates the limit for the definition of organ failure. HE: Hepatic encephalopathy; MAP: Mean arterial pressure; PaO₂: Arterial oxygen tension; FiO₂: Fraction of inspired oxygen; SpO₂: Peripheral capillary oxygen saturation.

Table 6 Degree of Acute on Chronic Liver Failure and the associated mortality

ACLF	Numbers of organ failure	28-d mortality	90-d mortality
0	0 or 1 (/kidney)	4.7%	15.0%
1	1 (no kidney dysfunction)	22.1%	40.7%
2	2	32.0%	52.3%
3	≥ 3	76.7%	79.1%

ACLF: Acute on Chronic Liver Failure.