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Resistin
1.
2. SERUM RESISTIN AS A PREDICTOR OF OUTCOME IN
TRAUMATIC HEAD- INJURED PATIENTS IN INTENSIVE
CARE UNIT OF SUEZ CANAL UNIVERSITY HOSPITAL
By
Hosam m atef ;MD
Anesthesia&ICU
3. Introduction
• The incidence of traumatic head injury is high in both industrialized and
non-industrialized countries and has been estimated variously to be
between150–250 cases per100,000 population per year.
• The Glasgow Coma Scale (GCS), the most commonly used system for
classification of traumatic head injury severity, grades a person's level of
consciousness on a scale of 3–15 based on verbal, motor, and eye-
opening reactions to stimuli. It is generally agreed that a traumatic head
injury with a GCS of 13 or above is mild, 9–12 is moderate, and 8 or
below is severe .
4. • Clinical and radiological tools for assessment of head injury severity and
predicting outcome lack sensitivity and specificity.
• Routinely performed CT in all patients with head injury may cause a
logistic and financial challenge in many emergencies unites.
• Identifying a high-risk group for adverse outcome after head trauma
would allow after care to be targeted at those with most to gain.
5. • High biomarker levels may also identify patients who are at highest risk
for secondary deterioration and who would benefit from repeat imaging,
monitoring, and increased surveillance.
• Resistin belongs to a novel family of cysteine-rich proteins called
resistin-like molecule or found in inflammatory zones proteins .
• In humans, resistin is expressed primarily in inflammatory cells,
especially macrophages. Furthermore, resistin has been shown to be
involved in inflammatory processes.
6. • However, it is evidenced that resistin could be produced by the brain and
pituitary gland.
• Furthermore, resistin mRNA was increased in the cortex of hypoxic,
ischemic and traumatic animal brain. In the patients with ischemic
stroke, high plasma resistin level has been associated with mortality and
disability.
• Recently, it is reported that high levels of resistin are present in the
peripheral blood of patients with intracerebral hemorrhage and are
associated with poor outcome.
7. Aim of the Work
The aim of this work is to study serum resistin
level as a predictor of outcome in ICU patients with
traumatic head injury in Suez Canal university
hospital. This is in a trial to improve outcome among
traumatic head - injured patients.
8. Patients and Methods
After obtaining approval by the Research Ethics Committee, a written
informed consent from the first degree relatives of patients was taken with an
explanation regarding the purpose, methods, effects, and complications.
Type of study :
• A prospective descriptive study.
Site of study :
• This study was held in ICU in Suez Canal University Hospital.
Target population:
• Patients attended to ICU in Suez Canal University Hospital, over one year with
severe head injury fulfilling the inclusion criteria were included in this study.
Sample size was 48 patients.
9. Inclusion criteria:
• History of traumatic head injury justified by Cranial Computed
Tomography (CCT) .
• GCS on admission : < 8/15 .
• Age : between 18 - 60 years old.
• Gender : both males and females .
10. Exclusion criteria:
• Pregnancy.
• Obesity (BMI >30kg/m2).
• Previous neurological disease.
• Patients with either of the following:
1) Diabetes Mellitus. 2) Hypertension.
3) Chronic heart disease. 4) Chronic lung disease.
5) Renal impairment. 6) Liver cirrhosis.
Methods of data collection:
This was done via questionnaire included the following data
1. Demographic data:
The patient’s age, gender, and BMI were recorded.
11. 2. Patient evaluation:
All patients were assessed clinically by:
(1) Medical History:
Detailed history from the patient's first degree relatives including:
- Mechanism of head injury. -Time of trauma.
-History of chronic illness. -History of any medications taken.
-Manifestations: vomiting, fits and disturbed level of consciousness
-History of previous neurological diseases and medications.
13. (3) Neurological assessment :
- Consciousness (Glasgow coma scale).
- Pupillary reflex.
- Signs of lateralization.
- Signs of fracture base of skull.
- Motor and sensory examination.
14. (4) Investigations including:
Laboratory:
– CBC, RBS
– PT, PTT, INR
– AST,ALT, total &direct bilirubin,
albumin
– Serum creatinine
– Serum Na+ ,K+ ,Ca++
– Serum level of resistin protein
– Arterial blood gases (ABG)
All samples were taken on admission and
according to the protocol of ICU
management till time of discharge from
ICU. Resistin samples were drawn only
on admission,3rdand 5th days.
Radiological Imaging:
- Chest X-ray
- Non-contrast brain CT
Others :
-Electrocardiography (strip ECG)
15. The procedures in ICU department :
1. Monitoring :
Vital signs including: BP , Pulse , SpO2.
Continuous temperature monitoring.
Daily monitoring of blood gases via ABG.
• We recorded dynamic parameters every 2hours over the 24hours then the mean
reading of them was taken in our study.
16. 2. Management :
-After cannulation , intubation was done using heavy sedation then
ventilation was done.
- Head up position 45 degree. - Deep sedation.
- Management of hyperthermia. - Adequate nutritional support.
- Peptic ulcer prophylaxis. - Proper glycaemic control.
- DVT prophylaxis. - Seizures control.
- Dehydrating measures.
17. • After collecting all the blood samples, analysis was done by the specific
resistin protein kits using ELISA .
End point
• Outcome was assessed as 14 days morbidity and mortality in ICU.
• Through Glasgow outcome scale (GOS).
• On discharge, survived patients were neurologically reassessed and ICU
length of stay was recorded.
18. Number Percentage
Age
20 – 24 50%
30 – 12 25%
40 – 48 12 25%
Mean ± SD 32.3 ± 8.1
Range 20 – 48
BMI
Mean ± SD 25.4 ± 2.7
Range 22.4 – 31.1
Table (1): Demographic characteristics among the studied patients:
Results
20. Table (2): Baseline clinical characteristics among the studied patients:
Number Percentage
Pupils react to
light
Both 16 33.3%
One 28 58.4%
None 4 8.3%
Signs of
lateralization
Present 8 16.7%
Absent 40 83.3%
Hypoxia
No 48 100%
Yes 0 0%
21. Table (3): Glasgow coma scale (GCS) among the studied patients on
admission and on follow up:
Mean ± SD Median (Range)
On admission 6 ± 1.3 b 5.5/15 (4/15 – 8/15)
On day 3 4 ± 1.9 a 4/10T (2/10T – 7/10T)
On day 5 5.6 ± 3.6 b 5.5/10T (2/10T – 15/15)
p-value 0.001*
22. Table (4): Hemodynamics and vital signs among the studied patients
on admission and on follow up:
On admission On day 3 On day 5 p-value
SBP(mmHg) 118.1 ± 16.9 a
127.3 ± 13.7
b
122 ± 7.4 a 0.004*
DBP(mmHg) 75.6 ± 10.5 a 75.4 ± 4.2 a 70.1 ± 6.6 b 0.001*
Mean arterial blood
pressure(mmHg)
87.5 ± 14.4 a 92.6 ± 6.6 b 87.5 ± 6.1 a 0.02*
Heart rate(beat/minute) 101.1 ± 22.5 a 95.8 ± 14.5 a 86 ± 15.5 b 0.001*
Respiratory
rate(cycle/minute)
18.1 ± 6.5 a 15.1 ± 3.3 b 14 ± 3.1 b 0.001*
Temperature(0C) 37.4 ± 0.6 a 36.9 ± 0.5 b 36.5 ± 0.5 b 0.001*
23. Table (5): CT findings on admission and follow up among the studied
patients:
Number Percentage
CT brain on admission
Fracture skull base 4 8.3%
Subdural hemorrhage 20 41.7%
Subarachnoid hemorrhage 12 25%
Severe brain edema 16 33.3%
Inter-ventricular hemorrhage 4 8.3%
Brain contusions 12 25%
Number of abnormality on
CT
Single finding 20 41.7%
Multiple abnormalities 28 58.3%
Finding of CT follow-up
No recent events 16 33.3%
Resolving 24 50%
New event 8 16.7%
24. Table (6): Serum resistin level (ng/ml) among the studied patients on
admission and on follow up:
Mean ± SD Median (Range)
On admission 0.79 ± 0.4 b 0.62 (0.413 – 1.82)
On day 3 1.34 ± 0.3 a 0.78 (0.425 – 1.45)
On day 5 0.75 ± 0.45 b 0.59 (0.321 – 1.92)
p-value 0.001*
28. Discussion
• In the model used in this study, multiple clinical and laboratory
variables have been used as predictors e.g. Glasgow coma scale
(GCS), pupil reactivity, hemodynamic and vital sign values, the
presence of a CT scan lesion, random blood sugar (RBS) and
serum resistin level.
• In a systematic review, Perel et al. in 2006 showed that GCS was
the most common predictor included in the models (50%)
followed by age (46%) and pupil reactivity (26%).
29. • In the current study, mortality at 14 days was 25% with a significant
difference between survival (36 patients) and non-survival group (12
patients) regarding mean age (29.1 and 34.5 years respectively), mean
GCS on admission (7.2/15 and 5.6/15 respectively), mean baseline
resistin level (0.69 and 1.12 ng/ml; p=0.03 respectively), mean RBS
(186.9 and 246.7 mg/dl respectively) and pupils reactivity. While pupils
were bilaterally reactive in 38.9% and unilaterally reactive in 61.1% in
the survival group patients, there were no reported cases with
nonreactive pupils. Pupils were bilaterally reactive in 16.7% and
unilaterally reactive in 50% in the non-survival group patients, while
there were 4 reported cases (33.3%) with nonreactive pupils.
30. • Similarly, Dong et al. in 2010 found that Twenty-six patients
(27.7%) died from TBI within 1 month. Baseline plasma resistin
level in the non-survival group was significantly higher than that in
the survival group (39.4 ± 12.4 vs. 23.8 ± 9.0 ng/mL; p< 0.001).
The neurological condition upon admission using GCS score and
unreactive pupils was statistically significantly different (both <
0.001) between the two groups. A higher proportion of patients in
the non-survival group suffered from hyperglycemia (p = 0.003).
31. • In the present study, multivariable predictive model for mortality at
14 days has shown that GCS on admission < 7/15, baseline
resistin level > 0.618ng/ml, RBS on admission > 200mg/dl and
nonreactive pupils on assessment are significant predictors while
age was not a significant predictor. Multiple logistic regression
model for poor GOS outcome has shown that GCS on admission
<7/15, unilaterally reactive pupil and baseline resistin level >
0.527 are significant .
32. • In the United States, Marshall et al. studied the relationship of
the initial GCS score with outcome and found the morality rate for
those with an initial post-traumatic GCS score of 3 was 78.4%;
initial GCS score of 4, 55.9%; and initial GCS score of 5, 40.2%.
of note, however, is that 4.1%, 6.3%, and 12.2% of the three
groups, respectively, had a good outcome.
• Dong et al. in 2010 introduced significant variables into
multivariate logistic model and selected GCS and plasma resistin
level as the independent predictors for 1-month mortality of
patients.
33. • In the present study, there is a significant correlation emerged
between plasma resistin level and GCS on admission, pupils
reactivity, mean arterial blood pressure and RBS. The present
study has also shown that a value of resistin level on admission
of TBI patient to ICU > 0.618 ng/ml was a significant predictor for
mortality at 14 days with sensitivity of 100%, specificity of 77.8%,
Positive predictive value of 60% and Negative predictive value of
100%( according to the ROC curve).
34. • Similar results in Dong et al. study in 2010, they found a
significant correlation between plasma resistin level and GCS
score on admission, pupils non-reactive on admission, and blood
glucose level ( p-value<0.02). A receiver operating characteristic
(ROC) curve identified plasma resistin cutoff level (30.8 ng/mL)
that predicted 1-month mortality with the optimal sensitivity
(84.6%) and specificity (75.0%) values ( P < 0.001) .
35. Conclusion
• A value of resistin level on admission of TBI patients to
ICU > 0.618 ng/ml is a significant predictor for 14 days
mortality with sensitivity of 100%, specificity of 77.8%,
PPV of 60% and NPV of 100%.
• Resistin could possibly used as a novel biomarker in TBI
as adjuvant prognostic tool to predict poor outcome.
36. Recommendations
• Use of resistin as a novel biomarker in TBI as adjuvant
diagnostic and prognostic tools to predict poor outcome.
Editor's Notes
Detailed history from the patient's first degree relatives including:
- Mechanism of head injury. -Time of trauma.
-History of chronic illness. -History of any medications taken.
-Manifestations: vomiting, fits and disturbed level of consciousness
-History of previous neurological diseases and medications.
