¹ LTMMC and LTMG Hospital & Medical College, Mumbai
² SIRO Research Foundation, Mumbai
³ Mucos Pharma GmbH, Geretsried, Germany

J Assoc Physicians India (JAPI) 2002, Vol. 50, pp. 527-531

Infections are a major cause of hospitalisation wherein the host mounts an inflammatory response  against the infecting agent. Administration of proteolytic enzymes could regulate the host's immune system and help early recovery from sepsis.
The aim of the study was  to test the efficacy and safety of an oral enzyme formulation, Phlogenzym (Mucos Pharma GmbH, Geretsried, Germany; constituents of each enteric - coated tablet were bromelain 90 mg, trypsin 48 mg, rutin 100 mg) as adjuvant therapy in treatment of sepsis in children.
Double-blind, randomised, controlled phase III study at a tertiary care center was performed wherein 60 eligible children aged one month to 12 years with sepsis were included. Detailed history, complete clinical evaluation including the modified Glasgow coma scale score, haemogram, bacterial culture, metabolic work up, liver and renal biochemistry were done in all cases. Cerebrospinal fluid analysis, urine analysis, radiological and other tests were done as and when needed to aid in di­agnosis. Patients were randomised to receive either Phlogenzym (n=30; 17 boys) or placebo (n=30; 22 boys) tablets (1 tablet / 10 kg body weight up to maximum six tablets a day in two or three divided doses for 14-21 days) along with appropriate antibiotics and supportive treatment. As the children were small and had altered conscious level, the tablets were crushed, mixed with ample water and given via an indwelling nasogastric tube and orally when the child was fully conscious. Dura­tion of treatment depended on the site and severity of infection. For children less than three months old, antibiotic combination used was ampicillin and gentamicin or cefotaxime and gentamicin or amikacin. Antibiotic combinations given to children older than three months were ampicillin and chloromycetin or ampicillin and cloxacillin and chloromycetin or cefotaxime and amikacin depending on the infecting agent and the se­verity of infection. Fourteen patients (six in Phlogenzym group) received dexamethasone in the first 3-5 days of the illness and five cases (two from Phlogenzym group) re­ceived phenobarbitone.
Median time taken for fever to subside was three days (range 1-12; 95% Cl - 1.14 to 7.14) in the Phlogenzym group vs four days (range 1-18; 95% Cl - 3.52 to 11.52) in the placebo group (p < 0.05); haemodynamic support was needed for two days (range 1-3; 95% Cl - 0.84 to 3.16) in the Phlogenzym group but three days (range 1-8; 95% Cl 0.76 to 5.24) in the placebo group (p < 0.05). The modified Glasgow coma scale score normalized in three days (range 1-14; 95% Cl 4.62 to 9.62) in the Phlogenzym group vs 5.5 days (range 1-18; 95% Cl - 2.52 to 13.52) in the placebo group (p > 0.05). Oral feeds could be started in four days (range 1-15; 95% Cl - 1.74 to 9.74) in the Phlogenzym group vs five days (range 1-11; 95% Cl - 1.26 to 11.26) in the placebo group (p > 0.05). Two patients died in the placebo group.
Patients in the study being very young and altered due to their illness had to be given crushed tablets. Gastric juice tends to dilute the enzymatic activity and this could have reduced efficacy of Phlogenzym. Fourteen patients (six in the Phlogenzym group) received dexamethasone which being immuno-suppressive would interfere with the enzyme functions. Nonetheless, the study suggests that enzymes have a place as an adjuvant with antibiotics and supportive treatment for early improvement of pediatric patients with sepsis.