Treatment with HELP-Apheresis Treatment with HELP-Apheresis in Patients Suffering from in Patients Suffering from

Sudden Sensorineural Hearing Loss: Sudden Sensorineural Hearing Loss: A Prospective, Randomized, Controlled StudyA 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 何何何 / VS 何何何

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ObjectiveObjective

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SSHL withhigh LDL

HELP-apheresis

Standard treatmen

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Standard treatmen

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IntroductionIntroduction 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

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IntroductionIntroduction

HELP apheresis: heparin induced LDL and fibrinogen precipitation◦ Improve hemorheology in pt with sudden

hearing lossIncreased RBC adhesiveness/aggregation owing to fibrinogen elevation in hypercholesterolaemic

patients and the rationale of fibrinogen-lowering by LDL apheresis. Eur J Clin Inv 2004;34:378-379

◦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

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IntroductionIntroduction

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

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MethodMethod

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%)

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MethodMethod 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

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MethodMethod 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%

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Evidence for maximal treatment of atherosclerosis: drastic reduction of cholesterol and fibrinogen restores vascular homeostasis. Ther

Apher 2001;5:207-211

MethodMethod

Prospective, randomized No placebo apheresis due to ethical

reasons◦Pt and investigators were not blinded◦Audiologists were blinded

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MethodMethod

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)

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ResultsResults

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ST HELP-ST

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• More hearing recovery in HELP-ST group• “Subsided pressure sensation of affected ear after

apheresis”.

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• HELP-ST group: significant at both [post] and [last] for all frequencies

• 250, 500, 1k Hz > 2k, 4k Hz• NS between [post] and [last].

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• HELP-ST better than ST• More evident at [post] and 250, 500, 2k Hz.

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• HELP-ST > ST.

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• Higher in fibrinogen<320

• Better recovery in fibrinogen <320.

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• HELP+ST as a choice for SSHL with fibrinogen>320.

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• HELP-ST better than ST, both period >8 or <8 days.

DiscussionDiscussion

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 LDLFibrinogen and LDL apheresis in treatment of sudden hearing loss: a randomised multicentre

trial. Lancet 2002;360:1811–1817.

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DiscussionDiscussion 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

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DiscussionDiscussion 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

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DiscussionDiscussion 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 >320Better in group of >320

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ConclusionConclusion 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

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