Treatment with HELP-Apheresis
in Patients Suffering from
Sudden Sensorineural Hearing Loss:
A Prospective, Randomized, Controlled Study
Bianchin G, Russi G, Romano N, Fioravanti P.
Otorhinolaryngology Unit , Santa Maria Nuova Hospital, Reggio
Emilia, Italy.
Laryngoscope. 2010 Jan 26
Ri 何佾昌/ VS 吳振吉
1
Objective
SSHL with
high LDL
HELPapheresis
Standard
treatment
Standard
treatment
2
Introduction
Sudden sensorineural hearing loss (SSHL)
◦ Mostly unilateral
◦ NIDCD: idiopathic hearing loss of ≧30dB over ≧3
contiguous test frequencies occurring within 3
days
Etiology:
◦
◦
◦
◦
Viral infection?
Autoimmunologic mechanism?
Rupture of inner ear membrane?
Disturbance of cochlear microcirculation
Blood flow ↓
Hyperviscosity: hypercholesteroleamia
3
Introduction
HELP apheresis: heparin induced LDL and
fibrinogen precipitation
◦ Improve hemorheology in pt with sudden
hearing loss
Increased RBC adhesiveness/aggregation owing to fibrinogen elevation in hypercholesterolaemic
patients and the rationale of fibrinogen-lowering by LDL apheresis. Eur J Clin Inv 2004;34:378379
◦ Circulating adhesion molecules (E-selectin,
VCAM-1, VCAM-1) reduced by apheresis
Does a reduction of adhesion molecules by LDL-apheresis have a role in the treatment of sudden
hearing loss? Ther Apher Dial 2006;10:282-286
4
Introduction
LDL/fibrinogen apheresis v.s. standard
treatment
◦ ST: prednisolone, hydroxyethyl starch,
pentixifylline
◦ Outcome: PTA, speech audiometry, tinnitus,
side effect
◦ Result: NS but better in apheresis group, esp
high LDL
Fibrinogen and LDL apheresis in treatment of sudden hearing loss: a randomised multicentrerial. Lancet
2002;360:1811–1817
5
Method
Pt selection
◦ Hearing symmetry before SSHL
◦ Inclusion:
Acute, one-side SSHL, ≦20 days before treatment
LDL > 120 mg/dL
◦ Exclusion:
Hx of hearing loss, Meniere’s dz, dz of middle ear
Tumor, heart dz, dialyzed, coagulopathy, allergy to
heparin, severe liver dz
◦ Superiority study (difference ≧30%)
6
Method
Standard treatment (ST)
◦ Glycerol 500ml IF QD ×10D
◦ Dexamethasone 8mg IM QD ×10D
HELP-apheresis
◦ 0.55μm plasma filter
◦ Mixed with 0.2M Na acetate buffer (pH 4.85)
containing 100 IU/mL heparin
◦ LDL and fibrinogen precipitates at pH 5.12
◦ 0.4μm polycarbonate filter
◦ Anion exchange absorber (remove at least 300000 IU
heparin)
◦ Bicarbonate dialysis + ultrafiltration
◦ 3L in 2hr, once
7
Method
HELP-apheresis
◦ TC -52%, LDL -56%, VLDL -52%, lipoprotein A 55%, TG -50%
◦ Fibrinogen -56%, thrombin -55%, VWF -56%,
FV -57%, FVII -35%
◦ CRP -56%, plasma viscosity -14%, RBC
aggregability -60%, thrombocyte aggregability
-60%
◦ HDL +14%, peripheral muscle oxygenation
+33~50%, coronary flow reserve +14%,
cerebral CO2 reactivity +14%
Evidence for maximal treatment of atherosclerosis: drastic reduction of cholesterol and
fibrinogen restores vascular homeostasis. Ther Apher 2001;5:207-211
8
Method
Prospective, randomized
No placebo apheresis due to ethical
reasons
◦ Pt and investigators were not blinded
◦ Audiologists were blinded
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Method
Acoustic measurement
◦
◦
◦
◦
[Pre]: admission day
[Post]: end of treatment
[Last]: 10 days after the end of treatment
Frequencies: 250, 500, 1k, 2k, 4k Hz
Outcome measurement
◦ Recovery percentage (%)
◦ Mean tonal threshold percentage (%)
◦ Decibel recovery (dB)
10
Results
ST
HELP-ST
11
• More hearing recovery in HELP-ST group
• “Subsided pressure sensation of affected ear after apheresis”.
12
• HELP-ST group: significant at both [post] and [last] for all
frequencies
• 250, 500, 1k Hz > 2k, 4k Hz
• NS between [post] and [last].
13
40%
40%
30%
HELP+ST
(post)
20%
ST
(post)
10%
0%
30%
HELP+ST
(last)
20%
ST
(last)
10%
0%
250
500
1k
2k
4k
250
500
1k
2k
4k
• HELP-ST better than ST
• More evident at [post] and 250, 500, 2k Hz.
14
25
25
20
20
15
HELP+ST
(post)
ST (post)
10
5
15
10
5
0
dB
HELP+ST
(last)
ST (last)
0
250
500
1k
2k
4k
dB
250
500
1k
2k
4k
• HELP-ST > ST.
15
60
25
50
fibrinogen
40
20
fibrinogen
30
>320 mg/dL
15
>320 mg/dL
20
<320 mg/dL
10
<320 mg/dL
10
5
0
0
250
500
1k
2k
4k
• Higher in fibrinogen<320
250
500
1k
2k
4k
• Better recovery in fibrinogen
<320.
16
15
HELP+ST (fibrinogen>320)
10
5
ST (fibrinogen>320)
0
250
500
1k
2k
4k
• HELP+ST as a choice for SSHL with fibrinogen>320.
17
• HELP-ST better than ST, both period >8 or <8 days.
18
Discussion
Disturbance of cochlear microcirculation
◦ Viremia → swelling of capillary endothelial
cell & mild hypercoagulation
◦ Increased viscosity → microcirculation↓
◦ Reduction of fibrinogen → viscosity↓ 20%
Haemorheology in defined dyslipoproteinemias with elevated serum triglyceride
concentrations. Atherosclerosis 1995;125:s117.
◦ HELP: pronounced improvement in pt with
high fibrinogen and LDL
Fibrinogen and LDL apheresis in treatment of sudden hearing loss: a randomised multicentre
trial. Lancet 2002;360:1811–1817.
19
Discussion
Plasma viscosity
◦ Inversely proportional to blood flow
◦ Hct, serum viscosity, RBC aggregation, RBC
deformability
◦ Low shear stress
↑Plt & macrophage adhesion, ↓NO, ↑plt &
endothelial growth factor
Interaction between RBCs
◦ Attraction: van der Waal force
◦ Repulsion: negative charge on RBC membrance
Counteract by LDL (30nm), fibrinogen (47nm)
HDL (10nm): competition with LDL
20
Discussion
HELP-apheresis: heparin for precipitation of
LDL and fibrinogen but totally absorbed later
→heparin not affect the outcome
Improvement > 30%
◦ HELP-ST: 75% [post], 76.4% [last]
◦ ST: 41.7% [post], 45% [last]
HELP-ST better than ST:
◦ All frequencies
◦ [post] or [last]
◦ % value or dB value
21
Discussion
HELP-ST better than ST
◦ No report of adverse reaction or side effect
Nausea/vomiting
Allergy to heparin
Wound infection, bleeding
◦ Pt: “I would receive apheresis again if hearing
loss recurred”
◦ No influence of fibrinogen on outcome
Improved Treatment of Sudden Hearing Loss by Specific Fibrinogen Apheresis. J Clin Apheresis
2004;19: 71–78.
Good recovery in both <320 or >320
Better in group of >320
22
Conclusion
HELP-apheresis is safe and effective
treatment for SSHL
◦ Especially high LDL and/or fibrinogen
◦ No complication
◦ Pt’s QoL better
(standardized SF36 questionnaire)
Rheopheresis for idiopathic sudden hearing loss: results from a large prospective, multicenter,
randomized, controlled clinical trial. Eur Arch Otorhinolaryngol 2009;266:943–953.
By studying this dz and its response to new
therapeutic approaches, we are able to gain
insight into pathophysiology of inner ear
23