5. 20%MANNITOL(SUGAR)VS3%SALINE(SALT)IN
CONTROLLINGICP
MANNITOL: lower ICP through creates a osmotic gradient across Blood Brain
Barrier,leadingtomovementofwater fromparenchymatointravascularspace
HYPERTONIC SALINE : HTS creates a osmotic shift of fluid from intracellular
space to interstitialandintravascularspace.
6. GOALS OF STUDY
• Toevaluatetheeffect of 20%mannitoland3% salinein pediatric acuteCNS
infection
• To compare which one has a better outcome over another in clinical
improvement
12. RANDOMIZATIONANDBLINDING
• Variable size blockrandomization
• A computer generated randomization list was generated by a person
blindedto protocol
• Statistician and clinical outcome assessors were blinded to
treatment assessment
14. GENERALCAREANDMONITORING
• Managementof raised ICPand mechanical ventilation were similar in both
groups
• ICPtransducerprobewasusedformonitoringofICP
• CerebralperfusionpressurewascalculatedasMAP-ICP
• On a average, 2 hrly monitored and ICP transducer probe removed when ICP
remainslessthan20mmHg continuouslyminimumof24hrs.
19. STATISTICALANALYSIS
• Statistical analyses were performed with SPSS software 20.0 (SPSS, Chicago, IL)
andEpi info 7(7.0.9.7;CenteforDiseaseControlandPrevention, Atlanta,GA)were
usedfordataanalysis
20. STATISTICALMETHODS
• ThetrendofMABPandICPandchange(delta–ICP),CPPandchange (delta-
CPP),Vasoactive score, vital signs,andlaboratoryvariables in the first 72hrs
between the groups were analyzed using general linear model repeated
measuresanalysisofvariance
• Time to event data ( resolution of coma, mechanical ventilation , ICP
transducer probe removal, death and PICU discharge )were analyzed using
Kaplan –Meier and log –rank test followed by cox regression analysis to
adjustforprespecifiedbaselinefactors(age, sex,diagnosis)andexpressedas
anadjustedhazardratiowith95% CI
21. • All test were two tailed, and a p value of less than 0.05 was taken as a
statisticallysignificant
26. SUMMARYOFRESULTS
PRIMARYOUTCOMES
Proportion of patient achieved the target average ICP (<20 mmHg)during
72hourswassignificantlyhigherinHTSgroup
MeanICPin the first 72hrs wassignificantly lower and CPP was higherin the
HTSgroup.
Mean delta- ICP was significantly more negative and mean delta- CPP was
significantlypositiveinHTSgroup
27. SECONDARYOUTCOMES
• Median (interquartile range) m-GCS score at 72hrs and at PICU discharge and
proportion of patients with m-GCS score ≥ 9 at above time points were
significantlyhigherinHTSgroup.
• In HTS group, proportion of patients who developed rebound raised ICP or
complications requiring temporary discontinuation or withholding osmotherapy
wassignificantlylowerthaninMannitolgroup.
• Proportion of patients who developed therapy related hypotension were
significantlylowerinHTSgroup.
• Severe hypernatremia (>160mEQ/l )was seen in higher number of patients in HTS
group
28. • FrequencyofAKI was similar in both groups
• Onepatientineachgrouphadevidenceofhaemolysis
• The coagulopathy (no clinical bleeding only lab evidence)was similar in both
groups
• On Kaplan Meir analysis, HTS group has a shorter median duration of
MechanicalventilationandPICUstay
29. • In the HTS group, three of six deaths (50%) were attributed to refractory
raisedICPincontrastto6of 10deathsinmannitolgroup(60%)
• At PICUdischarge, HTSgrouphas morenumberof patients with mildor no
neurodisability and significantly lesser number of patients with severe
disability
35. QUESTIONS COMMENTS YES NO
1.Did the study address
a clearly focused
question?
They clearly mentioned the population, and
intervention and the comparator was
chosen. The study tried to assess the
superiority of HTS vs mannitol as
osmotherapy
Yes
2. Was the assignments
of participant to
interventions
randomized ?
Randomization was carried out appropriately
with an view to eliminate systematic bias
Yes
3. Were all participants
who entered the study
accounted for at its
conclusion?
There were 52 participants who were not
been included in the conclusion as they are
not randomized
NO
36. QUESTIONS COMMENTS YES NO
4.Were the participants
‘blind’ to intervention they
were given
Yes
Were the investigators
‘blind’ to the intervention
they were giving to
participants?
NO
Were the people
assessing/analysing
outcome/s ‘blinded’
Yes
37. QUESTIONS COMMENTS YES NO
5.Were the study groups
similar at the start of the
randomised controlled
trial?
The baseline characteristics of each
study groups were similar and there are
no differences between the study
groups that could affect the outcome.
Yes
6.Apart from the
experimental
intervention, did each
study group receive the
same level of care?
There was clearly defined protocol and
the follow up intervals were similar for
each group
Yes
7.Were the effects of
intervention reported
comprehensively?
Yes
38. QUESTIONS COMMENTS YES NO
8.Was the precision of the
estimate of the intervention
of treatment effect
reported?
Confidence intervals were reported.
Yes
10. Would the
experimental intervention
provide greater value to the
people in your care than
any of the existing
Yes
Usual plasma osmolarity ranges between 280 and 295 mosm/ L, while HTS osmolarity vary from 1026 to 8008 mosm/L depending on HTS concentration (3-23.4%)
K-s test is used to decide if a sample comes from a population with a specific distribution
Chi-square test : to compare observed result with expected result.
Fisher exact test:analysis of contingency tables
Spss: statistical software suite developed by IBM
Epi info 7: statistical software developed by cdc in atlanta
Kaplan meir: used to measure the fraction of patients living for a certain amount of time after treatment.
Log rank : test the null hypothesis
Cox regression: predicts the value for the hazard and survival probability
