Table 2 Summary of inclusion criteria, IVIg preparation, dose and the control arm intervention in randomised clinical trials [63, 71, 138–152]
Study | Sepsis criteria and definitions used in IVIg trials | IVIg preparationa | IVIg dosing regime | Control |
|---|---|---|---|---|
Werdan et al. (2007) [63] | 1. At least 4 out of 9 components of sepsis criteria: temperature >38.5°C or <36°C; white blood cell count >12 × 109 l-1 or < 3.5 × 109 l-1; heart rate >100 minute-1; respiratory rate >28 minute-1 or fraction of inspired oxygen (FiO2) >0.21; mean arterial pressure <75 mmHg; cardiac index >4.5 l minute-1 m-2 or systemic vascular resistance <800 dyn s cm-5; platelet count <100 × 109 l-1; positive blood cultures; clinical evidence of sepsis (surgical or invasive procedure during the preceding 48 h or presence of an obvious septic focus). | Polyglobin N (Bayer Biological Products, Germany) | 0.6 g kg-1 on day zero 0.3 g. kg-1 on day one or two | 0.1% HAS |
| Â | 2) Sepsis score 12 to 27 | Â | Â | Â |
| Â | 3) APACHE II score 20 to 35 | Â | Â | Â |
Hentrich et al. (2006) [138] | ACCP/SCCM criteria and a diagnosis of haematological malignancy; neutropenia | Pentaglobin® (Biotest Pharma, Germany) | 1,300 ml over 72 h: 200 ml initially (0.5 ml minute-1) then 11 infusions 100 ml every 6 h | HAS |
Rodriguez et al. (2005) [139] | Severe sepsis/septic shock of intra-abdominal origin admitted to a critical care unit within 24 hours of onset of symptoms. Abdominal sepsis defined by the presence of SIRS and a surgically confirmed abdominal focus. Obtaining purulent material or detecting potential pathogens using Gram staining was mandatory. Appropriateness of the surgical procedure (successful eradication of focus), according to criteria of the attending surgical team and the intensivist, required for inclusion | Pentaglobin® (Biotest Pharma, Germany) | 0.35 g kg-1 day-1 | 5% HAS |
Darenberg et al. (2003) [71] | Streptococcal Toxic Shock Syndrome consensus definition | Endobulin SD (Baxter) | Loading dose of 1 g kg-1 then 0.5 g kg-1 every 24 h for three doses | 1% HAS |
Tugrul et al. (2002) [140] | Severe sepsis | Pentaglobin® (Biotest Pharma, Germany) | 5 ml kg-1 day-1 over 6 h | No treatment |
Karatzas et al. (2002) [141] | Severe sepsis | Pentaglobin® (Biotest Pharma, Germany) | 5 ml kg-1 day-1 over 6 h | No Treatment |
Masaoka et al. (2000) [142] | ACCP/SCCM criteria Suspected sepsis, as defined by heart rate >90 minute-1, respiratory rate >20 minute-1, in addition to positive C-reactive protein and sustained fever ≥38°C with | Not specified | 5 g day-1 for three consecutive days | No treatment |
| Â | a) specifi c infection: for example, respiratory tract infection such as pneumonia, urinary tract infection | Â | Â | Â |
| Â | b) no tumour, transfusion, drug-induced fever | Â | Â | Â |
| Â | c) blood culture negative | Â | Â | Â |
| Â | Patients were randomised if they were 'non-responders'- did not have enough improvement of symptoms with administration of broad-spectrum antibiotics for more than three consecutive days (72 h) | Â | Â | Â |
Dominioni et al. (1996) [143] | Sepsis following surgery or trauma with a Sepsis Score ≥17 | Sandoglobulin (Sandoz Pharmaceutical Corp, Italy) | 0.4 g kg-1 on day zero 0.4 g kg-1 24 h later 0.2 g kg-1 5 days later | 5% HAS |
Schedel et al. (1991) [144] | Detection of endotocaemia (>12.5 pg/ml endotoxin) and at least fi ve of the following criteria: clinical indications of septicaemia; fever ≥38.5°C; platelet count <100 × 109 l-1 or a 30% drop in last 24 h; shift to left in the blood count; granulocytopenia; pulmonary congestion; disseminated intravascular coagulation; systolic blood pressure <100 mmHg; heart rate >120 minute-1; urine output <500 ml day-1 | Pentaglobin® (Biotest Pharma. Germany) | Loading dose 600 ml over 8 h then two further doses of 300 ml every 24 h | No treatment |
Burns et al. (1991) [145] | 1. Platelet count <75 × 109 |-1 | Sandoglobulin (Sandoz Pharmaceutical Corp, Italy) | 0.4 g kg-1 day-1 | HAS |
| Â | 2. Documentation of suspected infection with positive culture | Â | Â | Â |
| Â | 3. Suspected infection documented by one or more of the following: fever; leukocytosis; elevated band neutrophil count; infiltrate on X-ray of chest consistent with pneumonia; toxic granulations or Dohle bodies on peripheral smear; positive Gram stain of body fluid or exudates | Â | Â | Â |
Wesoly et al. (1990) [146] | Post-operative sepsis with a Sepsis Score ≥12 | Pentaglobin® (Biotest Pharma, Germany) | 0.25 g kg-1 day-1 | No treatment |
Grundmann et al. (1988) [147] | Post-operative Gram-negative bacterial infection with positive endotoxin in plasma for two subsequent days and sepsis score >12 | Intraglobin F (Biotest Pharma, Germany) | 0.25 g kg-1 day-1 | No treatment |
De Simone et al. (1988) [148] | Severe sepsis | Sandoglobulin (Sandoz Pharmaceutical Corp, Italy) | 0.4 g kg-1 on day zero | No treatment |
| Â | Â | Â | 0.2 g kg-1 48 h later | Â |
| Â | Â | Â | 0.4 g kg-1 5 days later | Â |
Lindquist et al. (1981) [149] | Purulent meningitis irrespective of aetiology | Pepsis treated human gamma globulin -Gammavenin | 0.15 g kg-1 over 1 h | No treatment |
| Â | Suspected or verified bacterial pneumonia (day time admissions only) | Â | Â | Â |
| Â | Sepsis secondary to 'septicaemia' based on Svanbom criteria | Â | Â | Â |
Yakut et al. (1998) [150] | Post-surgical sepsis with Sepsis Score >16 | Gamumine N% 10 (Miles Inc. Pharmaceutical Division, USA) | 0.4 g kg-1 on day 0 | 20% HAS |
| Â | Â | Â | 0.4 g kg-1 on day 1 | Â |
| Â | Â | Â | 0.2 g kg-1 on days 2 to 7 | Â |
Behre et al. (1995) [151] | ACCP/SCCM criteria and a diagnosis of haematological malignancy; neutropenia | Pentaglobin® (Biotest Pharma, Germany) | Loading dose 10 g then 5 g six hourly for 72 h | 5% HAS |
Spannbruker et al. (1987) [152] | Septic shock | Pentaglobin® (Biotest Pharma, Germany) | 0.15 g kg-1 day-1 | No treatment |