Efficacy
and safety of Phlogenzym in sepsis in children – a randomized study
Shahid S.K.1
Turakhia N.H. 2 Kundra M. 1, Shanbag P. 1,
Daftary G.V. 2 Schiess W. 3. Efficacy and
safety of Phlogenzym - a protease formulation, in sepsis in
children. J Assoc Physicians India (JAPI) 2002, Vol. 50, pp.
527-531.
1 LTMMC and LTMG Hospital & Medical College, Mumbai. 2 SIRO Research
Foundation, Mumbai. 3 Mucos Pharma GmbH, Geretsried, Germany
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.