Table 2.
Studies reporting on the outcomes of IgM and IgA-enriched immunoglobin therapy
| References | Study design/enrolled patients | Cumulative dose | Outcome |
|---|---|---|---|
| Just et al. [54] |
Prospective, randomised, controlled clinical trial 104 intensive care patients (50 patients in treatment group, 54 patients in control group) |
Pentaglobin: initially 5 g, then 5 g every 12 h for 36 h (total 20 g) combined with antibiotics | There was a significant decrease in recovery time, ventilation time, and time spent in the ICU in the treatment group compared to the control group |
| Vogel [55] |
Prospective, randomized, controlled study 50 patients with sepsis (25 patients in treatment group, 25 patients in control group) |
Pentaglobin: 10 g/day for 3 days | There was a ~ 20% lower mortality rate in patients receiving Pentaglobin compared with the control group |
| Wesoly et al. [56] |
Prospective, randomized, controlled study 35 patients with septic postoperative complications (18 patients in treatment group, 17 patients in control group) |
Pentaglobin: 250 mg/kg/day | Endotoxin titers decreased, along with a reduction in mortality and shortening of hospitalization and mechanical ventilation time, in patients receiving Pentaglobin compared with control |
| Schedel et al. [57] |
Prospective, randomized, controlled clinical trial 55 patients with gram-negative septic shock (27 patients in treatment group, 28 patients in control group) |
Pentaglobin: for 3 days according to the following schedule: Day 1: 30 g over > 8 h; Days 2 and 3: 15 g over > 8 h | Patients treated with Pentaglobin had a significantly lower rate of sepsis-related mortality compared to the control group |
| Behre et al. [58] |
Prospective pilot study and randomized, controlled trial Pilot study: 21 patients with acute leukemia or non-Hodgkin’s lymphoma and sepsis syndrome Randomized controlled trial: 52 patients with hematological malignancies and sepsis syndrome (30 patients in treatment group, 22 patients in control group) |
Pentaglobin: Initial bolus of 10 g followed by 5 g every 6 h for 3 days | Patients treated with Pentaglobin had a significantly lower rate of all-cause 28-day mortality compared with those who received 5% human albumin |
| Rodríguez et al. [59] |
Multicenter, prospective, randomized, double-blind clinical trial 37 patients with abdominal sepsis (20 patients in treatment group, 17 patients in control group) |
Pentaglobin: 350 mg/kg/day for 5 days | There was no significant difference in organ dysfunction, organ failure, or mortality between the patients receiving Pentaglobin and the control group. The mortality rate was lower in the Pentaglobin versus control group without reaching statistical significance |
| Reith and Mittelkötter [60] |
Prospective, controlled trial 67 patients with severe sepsis or septic shock (35 patients in treatment group, 32 patients in control group) |
Pentaglobin: 15-20 g/day for 3 days | Patients treated with Pentaglobin had a significantly lower mortality rate compared with patients in the control group |
| Tugrul et al. [61] |
Prospective, randomized, controlled study 42 patients with severe sepsis (21 patients in treatment group, 21 patients in control group) |
Pentaglobin: 250 mg/kg/day over 6 h for 3 days | There was no significant difference in organ morbidity, septic shock incidence, or mortality between the treatment and control groups |
| Karatzas et al. [62] |
Prospective, randomized, controlled study 68 patients with severe sepsis (34 patients in treatment group, 34 patients in control group) |
Pentaglobin: 250 mg/kg/day over 6 h for 3 days | Patients treated with Pentaglobin had a significantly lower rate of 28-day mortality compared to the control group |
| Reith et al. [63] |
Prospective, randomized controlled study 64 patients with abdominal infection (31 patients in treatment group, 33 patients in control group) |
Pentaglobin: 10 g within 6 h of surgery followed by 55 g over the next 66 h by continuous perfusion (total: 1300 mL over 3 days) | There was no significant difference in incidence of fever, percentage of days with fever, mean body temperature, or duration of stay in hospital between those receiving Pentaglobin or albumin |
| Rodríguez et al. [64] |
Prospective, randomized, double-blind controlled study 56 patients with severe sepsis and septic shock of intra-abdominal origin (29 patients in treatment group, 27 patients in control group) |
Pentaglobin: 350 mg/kg/day for 5 days | There was a ~ 20% reduction in mortality rate in patients receiving Pentaglobin compared with the control group; however, there was no significant difference in organ dysfunction, organ failure, or mortality between the 2 groups |
| Buda et al. [65] |
Retrospective case-controlled study 66 patients diagnosed with sepsis after cardiac surgery (22 patients in treatment group, 44 patients in control group) |
Pentaglobin: 250 mg/kg daily for 3 days | Pentaglobin did not significantly reduce mortality in the overall study population. However, in the subgroup of patients with severe sepsis, it improved the survival rate significantly |
| Hentrich et al. [66] |
Multicenter, prospective, randomized, controlled study 206 neutropenic patients with sepsis syndrome or septic shock after receiving chemotherapy for severe hematologic disorders (103 patients in treatment group, 103 patients in control group) |
Pentaglobin: 65 g over 3 days according to the following schedule: 10 g initially (0.5 mL/min) followed by 11 infusions of 5 g, repeated every 6 h | There was no significant difference in all-cause 28- or 60-day mortality, or sepsis-related 28-day mortality between patients receiving Pentaglobin or human albumin |
| Yavuz et al. [67] |
Retrospective study 118 patients with sepsis-induced multiple organ dysfunction syndrome (56 patients in treatment group, 62 patients in control group) |
Pentaglobin: 250 mg/kg/day for 3 days | Patients who received IgM-enriched immunoglobulins had significantly lower overall mortality and 28-day case fatality rates and a shorter length of ICU stay compared with the control group |
| Toth et al. [68] |
Prospective, randomized, controlled pilot study 33 patients with early septic shock accompanied by severe respiratory failure (16 patients in treatment group, 17 patients in placebo group) |
Pentaglobin: 250 mg/kg over 8 h for 3 days | There was no significant difference in organ dysfunction between patients who received Pentaglobin and placebo |
| Brunner et al. [69] |
Prospective, randomized, double-blind, placebo-controlled trial 38 critically ill patients with multiple organ failure, systemic inflammatory response syndrome, and early clinical signs of critical illness polyneuropathy and/or myopathy (19 patients in treatment group, 19 patients in placebo group) |
Pentaglobin: 250 mg/kg body weight/day as a continuous intravenous infusion at a rate of 2 g/h for 3 days | Early treatment with Pentaglobin did not significantly improve critical illness polyneuropathy and/or myopathy or influence length of ICU stay or mortality in critically ill patients |
| Cavazzuti et al. [70] |
Retrospective cohort study 168 patients with septic shock (92 patients in treatment group, 76 patients in control group) |
Pentaglobin: 250 mg/kg/day (20 mg/kg/h) for 3 days | Early adjunctive treatment with IgM-enriched immunoglobulins resulted in an approximately 20% reduction in the absolute risk of 30-day mortality in patients with septic shock |
| Giamarellos-Bourboulis et al. [71] |
Retrospective analysis 200 patients with confirmed severe sepsis or septic shock caused by nosocomial multi-drug resistant Gram-negative bacteria infection (100 patients in treatment group, 100 in control group) |
Pentaglobin: Mean daily dose: 30 g/day administered as a 5–6-hour continuous infusion for 5 days | Patients treated with Pentaglobin had a significantly lower rate of all-cause 28-day mortality compared with the control group |
| Berlot et al. [72] |
Retrospective single-center study 355 patients with septic shock |
Pentaglobin: 250 mg/kg/day over 10 h for 3 days (total dose 750 mg/kg) | Earlier administration of Pentaglobin was associated with a decreased risk of in-ICU mortality, both in patients with septic shock caused by any pathogens and in patients with MDR-related septic shock |
| Willuweit et al. [73] |
Retrospective study 21 patients with sepsis-related vasoplegia post-liver transplant |
Pentaglobin: 250 mg/kg over 12 h for 3 days |
Patients who received IgM-enriched immunoglobulins had significantly decreased levels of inflammatory markers and a reduction in vasopressors required to maintain hemodynamic stability 30-day mortality was 14.3%, significantly less than calculated mortality (greater than 90%) based on Sepsis-Related Organ Failure Assessment scores |
| Domizi et al. [74] |
Single-center, randomized, double-blind, placebo-controlled Phase 2 trial 20 patients diagnosed with sepsis or septic shock for less than 24 h (10 patients in the treatment group, 10 patients in the control group) |
Pentaglobin: 250 mg/kg (5 mL/kg)/day for 3 days | A 72-hour infusion of Pentaglobin in patients with sepsis or septic shock was associated with an increase in sublingual microvascular perfusion |
Previous studies reporting on the outcomes of Pentaglobin therapy were identified by supplementing a recent publication which systematically searched PubMed, Cochrane Library, ISI Web of Knowledge, and Embase databases to update the 2013 edition of the Cochrane review from inception to June 2018 [52]. Their search strategy consisted of: [iviggma (All Fields) OR [igm (All Fields) AND enriched (All Fields)] OR [pentaglobulin (Supplementary Concept) OR pentaglobulin (All Fields) OR pentaglobin (All Fields)] AND [sepsis (MeSH Terms) OR sepsis (All Fields)]. We used the same search category in PubMed to complete the search from June 2018 to June 2020
ICU intensive care unit, IgA immunoglobulin A, IgG immunoglobulin G, IgM immunoglobulin M, MDR multidrug-resistant