Spontaneous bacterial peritonitis (SBP) may precipitate deterioration of circulatory function with severe hepatic insufficiency, hepatic encephalopathy, and type‐1 hepatorenal syndrome (HRS) and has 30% hospital mortality despite infection resolution.1 Predictors of this acute‐on‐chronic liver failure include ascitic fluid concentrations of granulocytes and cytokines and renal and hepatic insufficiency at diagnosis.1,2,3 Endotoxemia and the inflammatory response precipitate renal failure (RF) by accentuating splanchnic vasodilatation and impairing cardiac function.3,4,5 Compensatory activation of the renin‐angiotensin and sympathetic nervous systems further decrease renal perfusion. Volume expansion with albumin (1.5 g/kg day one, 1 g/kg day three) significantly reduces the incidence of HRS and hospital mortality.2
In the sole reported trial, only patients with serum bilirubin (bili) >68.4 μmol/l, blood urea nitrogen (BUN) >30 mg/dl or serum creatinine (Cr) >88.4 μmol/l appeared to benefit from albumin.2 In this report we describe a therapeutic protocol involving 38 episodes in 28 patients at the Mount Sinai Medical Center New York and the Barcelona Hospital Clinic in which albumin (1.5 g/Kg on the day of diagnosis, 1 g/Kg on the third day; Human Albumin 25%, ZBL Bioplasma AG, Berne, Switzerland) was restricted to those at high risk for RF (bili > 68.4 μmol/l or Cr >88.4 μmol/l) (table 1). Diagnosis and treatment of SBP were based on established guidelines.6 Cardiovascular and splanchnic hemodynamics and the activity of the renin‐angiotensin system and inflammatory response were assessed in 6 low‐risk cases from Barcelona at SBP diagnosis and resolution.3,7,8
Table 1 Clinical characteristics of patients at diagnosis of spontaneous bacterial peritonitis episodes who did receive (A) and who did not receive (B) albumin.
| A (n = 26) | B (n = 18) | p Value | |
|---|---|---|---|
| Age (years) | 50 (32–70) | 54 (38–74) | 0.383 |
| Sex (male/female) | 12/14 | 12/6 | 0.179 |
| Aetiology (HCV/other) | 12/14 | 12/6 | 0.179 |
| History of SBP (n/%) | 15 (58%) | 7 (39%) | 0.220 |
| SBP prophylaxis (n/%) | 10 (39%) | 6 (33%) | 0.728 |
| Community/hospital acquired SBP (n) | 19/7 | 15/3 | 0.489 |
| Mean arterial pressure (mm Hg) | 78 (54–124) | 88 (62–103) | 0.046 |
| Hepatic encephalopathy | 23 (89%) | 9 (50%) | 0.007 |
| Total bilirubin (μmol/l) | 115 (12–395) | 39 (14–67) | <0.001 |
| Albumin (g/dl) | 2.1 (1.5–3.5) | 2.2 (0.8–4.1) | 0.005 |
| INR | 2.3 (1.2–5.9) | 1.7 (1.1–2.2) | 0.002 |
| BUN (mg/dl) | 28.5 (7–74) | 18 (5–48) | 0.003 |
| Creatinine (μmol/l) | 124 (35–327) | 80 (53–106) | 0.001 |
| White cell count (×103/μL) | 9.4 (2.7–34.3) | 7.5 (2.5–17.5) | 0.010 |
| Ascitic neutrophil count (/μL) | 1464 (128–21794) | 833 (90–8640) | 0.062 |
| Child‐Pugh score | 13 (9–15) | 10 (8–12) | <0.001 |
| MELD score | 26 (14–42) | 14 (6–18) | <0.001 |
BUN, blood urea nitrogen; HCV, Hepatitis C Virus; INR, interleukin; MELD, model end‐stage liver disease; SBP, spontaneous bacterial peritonitis
In the low‐risk group (15 patients, 18 episodes), SBP resolved in all, and none developed RI. None of the 15 patients died. In the subgroup in which hemodynamic assessment was performed, the characteristic profile of severe portal hypertension and hyperdynamic circulation was present, and the only change at resolution was a decrease in plasma renin activity (table 2).
Table 2 Systemic and splanchnic hemodynamics, endogenous vasoactive systems and interleukin 6 at spontaneous bacterial peritonitis diagnosis and resolution.
| Diagnostic | Resolution | p Value | |
|---|---|---|---|
| Cardiac index (L/min/m2) | 5.0 (3.3–6.4) | 3.9 (3.7–5.3) | 0.094 |
| Systolic volume (ml) | 93 (67–131) | 83 (63–114) | 0.188 |
| Heart rate (bpm) | 83 (71–127) | 80 (58–112) | 0.313 |
| Right atrial pressure (mm Hg) | 8 (4–11) | 7 (5–11) | 0.875 |
| Pulmonary artery pressure (mm Hg) | 17 (13–28) | 18 (14–29) | 0.438 |
| Pulmonary capillary pressure (mm Hg) | 11 (7–19) | 11 (9–13) | 0.625 |
| Systemic vascular resistance (dyn/s/cm5) | 668 (467–1153) | 852 (706–970) | 0.438 |
| Mean arterial pressure (mm Hg) | 80 (70–89) | 79 (67–88) | 1.000 |
| Wedged hepatic venous pressure (mm Hg) | 32 (25–37) | 31 (24–40) | 0.875 |
| Free hepatic venous pressure (mm Hg) | 10 (8–14) | 12 (6–15) | 0.313 |
| Hepatic venous pressure gradient (mm Hg) | 20 (17–29) | 19 (13–35) | 0.625 |
| Hepatic blood flow (l/min) | 1.0 (0.5–1.7) | 0.7 (0.4–2.0) | 0.688 |
| Plasma renin activity (ng/ml/h) | 5.6 (0.5–8.1) | 3.1 (0.1–5.8) | 0.031 |
| Norepinephrine (pg/ml) | 257 (172–805) | 255 (44–511) | 0.156 |
| Plasma IL6 (pg/ml) | 65 (8–365) | 16 (10–63) | 0.625 |
| Serum NOx (nmol/ml) | 35 (24–40) | 30 (21–55) | 1.000 |
| Ascitic fluid NOx (nmol/ml) | 30 (12–68) | 33 (32–93) | 0.125 |
Nox, nitric oxide; IL, interleukin.
In the high‐risk group (21 patients, 26 episodes), renal impairment (RI) was present in 12 patients (57%) and 15 episodes (58%). It resolved in 10 episodes, remained steady in three, and progressed in two. Among 11 episodes with normal renal function, it remained normal in nine and progressive RF developed in two. RF responded in two episodes to a vasoconstrictor (midodrine, noradrenaline) and albumin but subsequently recurred. In two episodes, RF developed after SBP resolution. The outcome in five (24%) patients (19% episodes) was death.
This study is the first to assess whether albumin is needed for all cases of SBP. Our results indicate that patients with bili <68.4 μmol/l and Cr <88.4 μmol/l can be treated without albumin. Hemodynamic deterioration did not develop in these low‐risk episodes. Plasma renin activity, the most sensitive marker of effective arterial blood volume, also decreased, indicating improvement in effective hypovolemia and providing additional support for our proposal that albumin need not be administered to all patients. Although our results do not provide definite proof because of the absence of a control group, they do provide supportive evidence for the role for albumin in patients at high risk of acute‐on‐chronic liver failure. Fifteen of 26 high‐risk episodes had RI at diagnosis. According to previous reports, 50% hospital mortality rate should have been expected.2,9
An explanation for the discriminative power of Cr and bili remains to be determined. Elevated levels prior to infection would indicate that patients with pre‐existing advanced cirrhosis and impaired renal function are predisposed to the development of HRS. Alternatively, individual response to infection would be of pathophysiologic significance. Despite the beneficial effect of albumin, treatment of SBP is still not optimal, and RF may still develop. Whether co‐administration of a vasoconstrictor would further prevent the development of RF remains to be determined.
Acknowledgements
Dr C.M. Stanca was supported by the Artzt Family Charitable Trust.
Footnotes
Competing interests: None.
References
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