The Impact of IVIG Treatment on Critical Illness Polyneuropathy and/or Myopathy in Patients With MOF and SIRS/Sepsis
The Impact of IVIG Treatment on Critical Illness Polyneuropathy and/or Myopathy in Patients With MOF and SIRS/Sepsis
Critical illness polyneuropathy and/or myopathy (CIPNM) is a severe complication of critical
 illness. Retrospective data suggest that early application of IgM-enriched intravenous
 immunoglobulin (IVIG) may prevent or mitigate CIPNM. Therefore, the primary objective was to
 assess the effect of early IgM-enriched IVIG versus placebo to mitigate CIPNM in a
 prospective setting.
Background: Critical illness polyneuropathy and/or myopathy (CIPNM) is a severe complication
 of critical illness. Retrospective data suggest that early application of IgM-enriched
 intravenous immunoglobulin (IVIG) may prevent or mitigate CIPNM. Therefore, the primary
 objective will be to assess the effect of early IgM-enriched IVIG versus placebo to mitigate
 CIPNM in a prospective setting.

 Design: Prospective, randomized, double-blinded and placebo-controlled trial

 Setting: Eight-bed medical ICU of a university hospital.

 Participants: Critically ill patients will be screened for eligibility defined as multiple
 organ failure (MOF) and SIRS/sepsis. Patients fulfilling these criteria will be further
 assessed by a neurologist for clinical signs of CIPNM.

 Critically ill patients with multiple organ failure (MOF), SIRS/sepsis, and early clinical
 signs of CIPNM will be randomized.
Inclusion Criteria:

 Critically ill patients with failure of at least 2 organ systems diagnosed with SIRS or
 sepsis fulfilling the following inclusion criteria will be included in this study.

 1. Age Range: 18 - 80 years

 2. written information and consent as early as possible

 3. Male and female patients

 4. Clinical signs of incipient CIPNM:

 -  decreased tendon reflexes as compared to the admission examination at the ICU

 -  or weakness in responsive and co-operative patients as compared to the ad-mission
 examination at the ICU

 -  or signs of incipient muscular atrophy as compared to the admission examination
 at the ICU

 Organ failure:

 Patients have to meet at least two of the following 5 criteria:

 -  cardiovascular system dysfunction: arterial systolic blood pressure<90mm Hg, or mean
 arterial pressure < 70mm Hg for at least one hour despite adequate fluid
 resuscitation, adequate intravascular volume status or the use of vasopressors in an
 attempt to maintain a systolic blood pressure >90mm Hg or a mean arterial pressure
 >70mm Hg.

 -  kidney dysfunction: Urine output < 0,5ml/kg body weight/ hour for 1 hour, despite
 adequate fluid resuscitation

 -  respiratory system dysfunction: Ratio of PaO2 to FiO2 < 250 in the presence of other
 dysfunctional organs or systems

 -  hematologic dysfunction: Platelet count <80.000/mm3 or decreased by 50% in the 3 days
 preceding enrollment (in the absence of liver cirrhosis or previously known
 hematological disease)

 -  metabolic dysfunction: In case of unexplained metabolic acidosis - pH<7,30 or base
 deficit >5.0mmol/ litre in association with a plasma lactate level >1,5 times of the
 upper normal limit

 SIRS:

 Patients have to meet at least three of the following four criteria:

 -  core temperature >38 or <36°C

 -  heart rate >90 beats /min, except medical conditions known to increase heart rate

 -  respiratory rate >20 breaths/min or a PaCO2 of <32mm Hg or the use of mechanical
 ventilation for an acute respiratory process

 -  a white- cell count of>12.000 cells/mm3 or <4.000 cells/mm3 or a differential count
 showing >10% immature neutrophils

 Sepsis:

 Known or suspected infection evidenced by one or more of the following:

 -  white cells or bacteria in a normally sterile body fluid

 -  perforated viscus

 -  radiographic evidence of pneumonia in the association with the production of purulent
 sputum

 -  a syndrome associated with a high risk of infection

 Exclusion Criteria:

 The inclusion criteria have to be met at the time of enrolment into the study, i.e. at the
 start of the baseline period. Patients with any of the following conditions will be
 excluded from the study:

 1. Age < 18 years or > 80 years

 2. Weight >135 kg

 3. Pregnancy or breast-feeding

 4. Patients with known absolute IgA-deficiency with proven antibody formation against IgA

 5. Patients with known IVIG-intolerability

 6. Patients with known pre-existing neuromuscular disorders will not be included.
 Patients with documented pre-existing severe polyneuropathy will be excluded.

 7. Patients with known diseases of the peripheral nerval system and patients with
 pre-existing disease of the central nerval system with relevant impairment of the
 motor function.

 8. Patients with relevant pulmonary edema secondary to severe heart failure will be
 excluded because of the relatively high infusion volume (5ml /kg body weight per day
 over 3 days) determined by the study medication

 9. Patients not expected to survive 28 days because of uncorrectable medical condition,
 such as poorly controlled neoplasma or other end-stage disease

 10. Moribund state in which death is perceived to be imminent

 11. HIV infection in association with a last known CD4 count of<50/mm3

 12. Prediction, based on clinical judgement, that the patient will require chronic
 ventilatory support for non-respiratory reasons (e.g. neuromuscular disease,
 paraplegia