plasmapheresis in icu

Plasmapheresis in critical care

Dr.Ahmed Balshi Medical Consultant, MD, ABIM, SB-Med, ICU FellowDr. Muhammad Asim RanaMBBS, MRCP, MRCPS, FCCP, EDIC, SF-

CCM ICU Consultant

Objectives Terminology. To understanding plasmapheresis. Review of the (ANN) American Academy of

Neurology Recommendations. Review of (ASFA) The American Society for

Apheresis / (AABB) The American Association of Blood Banks) guidelines.

BMJ best practice recommendations. Case presentation.

TERMINOLOGY

Apheresis : An umbrella term for "taking away" a blood component. From Roman aphairesis meaning to take away by force.

Plasmapheresis : A general term used to denote the automated, selective removal of plasma. Plasmapheresis uses centrifugation to separate the blood components, in contrast to dialysis, which uses filtration to separate small molecules from the blood.

Plasma exchange (also called therapeutic plasma exchange [TPE]) Removal of patient plasma and replacement with another fluid (eg, donor plasma, colloid, crystalloid).

TERMINOLOGY

Hemapheresis (also called cytapheresis) – A term used to denote selective removal of abnormal blood cells or excessive numbers of cells.

Dialysis – A diffusion-based treatment best suited for the removal of fluid or small molecules (eg, uremic toxins, some drugs) from the blood using a filter.

Plasma filtration – A technique that separates plasma from cellular components with a highly permeable filter (plasma filter) using a dialysis or hemofiltration machine.

Therapeutic Plasma Exchange

Therapeutic Plasma Exchange

The basic of (TPE) is that removal of certain pathologic substances from the plasma will reduce further damage and may permit reversal of the pathologic process.

The process involves the removal of most or all of the patient’s plasma, by passing venous blood through an extracorporeal continuous flow centrifugation device.

This device separates blood into its components, shunts some or all of the plasma into a discard container, and returns most of the remaining blood to the patient, along with a short-acting anticoagulant (usually citrate).

PRESCRIPTION

The following formula can be used to Estimate the plasma volume in an adult:

Estimate plasma volume (in liters) = 0.07 x weight (kg) x (1 -

hematocrit)

For most conditions in which plasmapheresis is used, it is considered acceptable to perform 1 to 1.5 plasma volume exchanges per procedure

Technique :Plasma exchange is most commonly performed with centrifugation devices used in blood banking procedures. These devices also offer the advantage of allowing selective cell removal (cytapheresis).

Venous access : Successful execution of a therapeutic plasma exchange (TPE) procedure requires reliable venous access, which may be either two large durable peripheral veins or central line.

Apheresis schedule

The AABB general recommendation is that one exchange be performed every 2nd or 3rd day, each exchange consisting of 1 to 1.5 plasma volumes, for a total of 3 to 5 procedures.

Exceptions include the following:*In acute GBS, it may be necessary after the initial exchanges

to perform TPE one to two times a week until improvement occurs.

*In TTP, plasma exchanges should be performed daily until the platelet count is normal for two to three consecutive days.

*Treatment for Goodpasture's syndrome (anti-GBM mediated disease) is generally also performed on a daily basis for at least two weeks.

AABB: American Association of Blood Banks

Replacement fluids

Albumin, saline, or a combination of albumin and saline, are the replacement fluids of choice for most conditions. It is generally recommended that plasma only be used as the replacement fluids for TTP, (TTP-HUS), or thrombotic microangiopathy (TMA).

5% Albumin : Albumin has the advantages of lack of viral transmission and minimal risk of anaphylactic reactions.

Albumin-saline combination : When colloid and crystalloid solutions are used in combination, the amount of colloid should not be <50% of the total infused. An appropriate replacement solution would consist of 60 to 80% colloid and 20 to 40% saline .

Plasma : Plasma can be provided in the form of FFP, plasma frozen 24 hours after collection (FP24).

Cytapheresis

Cytapheresis aims to lower the leukocyte, platelet, erythrocyte count.

The post-procedure target WBC count in hyperleukocytosis is < 100,000

For thrombocytosis, the target platelet count is < 1,000,000

Cytapheresis of red blood cells can be done for the following: Removing red blood cells in patients with polycythemia or iron

overload. Exchange transfusion to prevent or treat complications of SCD

(stroke) or for vasoocclusive pain events (sickle cell crisis). In crisis, the goal is the removal of more than 50% of hemoglobin S, and it monitored by measuring the Hgb concentration and percent hemoglobin S.

Severely parasitemic conditions, such as malaria and babesiosis, in order to promote response to pharmaceutical management.

Complications

HYPOTENSION TRANSFUSION-RELATED ACUTE LUNG INJURY CITRATE-INDUCED HYPOCALCEMIA CITRATE-INDUCED METABOLIC ALKALOSIS COAGULATION ABNORMALITIES INFECTION VIRAL TRANSMISSION BY PLASMA ANAPHYLACTIC REACTIONS TO PLASMA HYPOKALEMIA PROBLEMS WITH VASCULAR CATHETERS

MORTALITY: 0.03 % to 0.05 %, Respiratory or Cardiac complications were most common.

Evidence Based Guidelines

ANN/ASFA/AABB/BMJ

AAN Guideline ProcessClinical Question

Evidence

Conclusions

Recommendations All studies rated Class I, II, III, or IV © 2011 AMERICAN ACADEMY OF NEUROLOGY

AAN Level of Recommendations

• A = Established as effective, ineffective or harmful.• B = Probably effective, ineffective or harmful.• C = Possibly effective, ineffective or harmful.• U = Data inadequate or conflicting; given

current knowledge, treatment (test, predictor) is unproven.

Note that recommendations can be positive or negative.

© 2011 AMERICAN ACADEMY OF NEUROLOGY

Question 1: What is the efficacy of plasmapheresis in the treatment of AIDP, also known as GBS?

2011 AMERICAN ACADEMY OF NEUROLOGY

Conclusion: Plasmapheresis is established as effective for

the treatment of AIDP/GBS severe enough to impair the ability to walk independently or severe enough to require mechanical ventilation.

Recommendation: Plasmapheresis should be offered in the

treatment of AIDP/GBS severe enough to impair independent walking or to require mechanical ventilation (Level A).


Conclusion: For milder AIDP/GBS, in which ambulation is

preserved, plasmapheresis is probably effective.

Recommendation: Plasmapheresis should be considered in the

treatment of milder clinical presentations of AIDP/GBS (Level B).

© IV immunoglobulin (IVIG) is an alternative treatment used in patients with AIDP/GBS. There is insufficient evidence to demonstrate the superiority of one treatment over the other.


Question 2: What is the efficacy of plasmapheresis in the treatment of CIDP?


Conclusion: Plasmapheresis is established as effective in the

short-term treatment of CIDP; both studies showed the beneficial effect is not sustained, with worsening beginning 1 to 5 weeks after last plasmapheresis treatment.

Recommendation: Plasmapheresis should be offered as a short-

term treatment for patients with CIDP (Level A).© Steroids, IVIG, and immunosuppressants have

also been used in the treatment of CIDP. © 2011 AMERICAN ACADEMY OF NEUROLOGY

Question 3: What is the efficacy of plasmapheresis in the treatment of MG?


Conclusion: There are inadequate data to evaluate the use

of plasmapheresis in the treatment of myasthenic crisis or in the treatment of MG prethymectomy.

Recommendation: Because of the lack of randomized controlled

studies with masked outcomes, there is insufficient evidence to support or refute the efficacy of plasmapheresis in the treatment of myasthenic crisis (Level U) or MG prethymectomy (Level U).


Clinical Context Despite the fact that the use of

plasmapheresis in myasthenic crisis and MG prethymectomy receives a Level U recommendation, plasmapheresis is still used at many medical centers for these indications.


Question 4: What is the efficacy of plasmapheresis in the treatment of dysimmune neuropathies?


Conclusion: Plasmapheresis is probably effective in IgA- and

IgG- monoclonal gammopathy of undetermined significance (MGUS)-associated polyneuropathy.

Recommendation: Plasmapheresis should be considered in

polyneuropathy associated with IgA and IgG MGUS (Level B).


Conclusion: Plasmapheresis is probably not effective in

polyneuropathy associated with IgM MGUS.

Recommendation: Plasmapheresis should not be considered in

the treatment of polyneuropathy associated with IgM MGUS (Level B).


Question 5: What is the efficacy of plasmapheresis in the treatment of CNS demyelinating disease (MS) ?


Conclusion: Plasmapheresis as adjunctive therapy is

probably effective for management of exacerbations in relapsing forms of MS.

Recommendation: Plasmapheresis should be considered for the

adjunctive treatment of exacerbations in relapsing forms of MS (Level B).


Conclusion: Plasmapheresis is possibly effective for acute

fulminant CNS demyelinating diseases (including MS, acute disseminated encephalomyelitis [ADEM], neuromyelitis optica [NMO], and transverse myelitis [TM]) that fail to respond to high-dose corticosteroid treatment.

Because the study included subgroups of patients with demyelinating diseases, it is not possible to determine if plasmapheresis is more or less effective in patients with different demyelinating diseases.


Recommendation: Plasmapheresis may be considered in the

treatment of fulminant CNS demyelinating diseases that fail to respond to high-dose corticosteroid treatment (Level C).


Conclusion: For chronic progressive or secondary

progressive MS, plasmapheresis is established as ineffective based on consistent Class I evidence.

Recommendation: Plasmapheresis should not be offered for

chronic progressive or secondary progressive MS (Level A).


GENERAL THERAPEUTIC CATEGORIES

(ASFA) / (AABB) guidelines for TPE are based on extensive literature reviews. These guidelines are generally updated every two or three years (last update 2013). Conditions are divided into four categories, based on evidence of clinical efficacy of TPE reported in reviewed literature.

Category I: Disorders for which apheresis is accepted as 1st line therapy.

Category II: Disorders for which apheresis is accepted as 2nd line therapy.

Category III: Disorders for which the optimum role of apheresis therapy is not established.

Category IV: Disorders for which published evidence demonstrates or suggests apheresis to be ineffective or harmful.

ASFA :The American Society for Apheresis. AABB: The American Association of Blood Banks

Category I Plasma exchange

GBS as first-line stand alone therapy. CIDP. Hyperviscosity in monoclonal gammopathies. ANCA-associated rapidly progressive glomerulonephritis

(Wegener's). Anti-GBM disease (Goodpasture's syndrome). Severe Cryoglobulinemia. FSGS (Recurrent in transplanted kidney). HUS (Atypical HUS due to autoantibody). TTP. MG (Moderate-severe ,Pre-thymectomy). Wilson disease, fulminant.

Category I

Red blood cell exchange (ie, exchange transfusion) in sickle cell disease for the management of acute stroke.

Red blood cell exchange :Severe Babesiosis.

Erythrocytapheresis: Hereditary hemochromatosis, Polycythemia vera.

Leukocytapheresis: Leukostasis

Category II Plasma exchange

Secondary treatment for acute disseminated encephalomyelitis after high-dose intravenous corticosteroid failure.

Autoimmune hemolytic anemia (life-threatening cold agglutinin disease).

Antiphospholipid syndrome, catastrophic. Multiple sclerosis. Myeloma cast nephropathy. Neuromyelitis optica (Devic's syndrome), acute. Overdose, Venoms, and Mushroom poisoning. SLE, severe (eg, cerebritis, diffuse alveolar

hemorrhage).

Category II

Red blood cell exchange for acute chest syndrome in sickle cell disease.

Red blood cell exchange for severe Malaria. Thrombocytapheresis: Symptomatic

Thrombocytosis.

Category III Plasma exchange

Aplastic anemia. Immunoglobin A nephropathy. Hypertriglyceridemic pancreatitis. Chronic progressive Multiple sclerosis. Severe Pemphigus vulgaris. Post-transfusion purpura. Scleroderma (progressive systemic sclerosis). Sepsis with multiorgan failure. Thyroid storm.

Category III

Erythrocytapheresis: Secondary erythrocytosis.

Leukocytapheresis: Hyperleukocytosis , Prophylaxis.

Lymphocytapheresis: Psoriasis .

Thrombocytapheresis: Thrombocytosis, Prophylactic or secondary.

Category IV Plasma exchange

Active rheumatoid arthritis. Amyotrophic lateral sclerosis. Dermatomyositis, polymyositis. Inclusion body myositis. Immune thrombocytopenia, refractory. POEMS syndrome.

Guillain-Barre syndrome

● Both plasma exchange and intravenous immunoglobulin (IVIG) have been shown to be equally efficacious. The choice between them is often institution-dependent.● The dose for plasma exchange is given through a central venous catheter every other day for 7 to 14 days.

Chronic inflammatory demyelinating

polyradiculoneuropathy Initial monotherapy: IVIG, corticosteroids, or plasma

exchange.

Approximately 75% to 85% of patients will respond to monotherapy with intravenous immunoglobulin (IVIG), corticosteroids, or plasma exchange. While there are several trials showing similar efficacy, there is no consensus as to which is the preferred treatment, and all have been advocated as initial therapies.

Methylprednisolone: 1000 mg iV once daily for 3-5 days, followed by 1000 mg once weekly until clinical response (usually 4-12 wks)

Dexamethasone: 40 mg PO once daily for 4 days every 4 weeks for 6 months Prednesolone:. 0.5 to 1 mg/kg/day PO until clinical response (usually 4-12 wks) IV IG : 2000 mg/kg/dose iV, given as either 400 mg/kg once daily for 5 consecutive days, or 1000

mg/kg for two consecutive days; repeat every 2-4 weeks depending on response

MS,acute relapse affecting function

1st Line :Methylprednisolone: 1000 mg iv once daily for 3 days

2nd Line :IV IG Can be used if methylpredisolone is ineffective or contraindicated (e.g., in patients with infection, poorly controlled diabetes, or hypertension).

Plasma exchange :When a patient becomes quadriplegic over days to weeks, plasma exchange has been shown to be effective in some patients and is used in severe cases.

Myasthenia gravis Severe disease (myasthenic crisis): 1st intubation and mechanical ventilationplus plasma exchange ( 1 to 1.5 plasma volume during

each of 5 treatments daily or on alternate days over 2 week period) or IVIG (400 mg/kg/day iv for 5 days).

plus supportive careNote :Plasma exchange has rapid response with onset usually

after 2 to 3 sessions. Effects are temporary, lasting weeks.

Lambert-Eaton myasthenic syndrome

Severe respiratory or bulbar weakness 1st intubation and mechanical ventilation plus plasma exchange or (IVIG) . plus supportive care.

Note :Plasma exchange or high-dose IVIG may be used to induce relatively rapid but transient improvement in symptoms.

Haemolytic uraemic syndrome

Epidemic HUS: adults 1st Line plasma exchange. Sporadic and secondary HUS: not due to S.

pneumoniae 1st Line plasma exchange. Sporadic and secondary HUS: due to S

pneumoniae 1st Line antibiotic therapy.

Thrombotic thrombocytopenic purpura

Acute episode 1st Line plasma exchange.The mortality rate prior to the use of

plasma exchange was as high as 90% .

PLASMA EXCHANGE : The efficacy of plasma exchange in the treatment of TTP in

adults has been demonstrated in two trials that included 210 patients. The results of these studies can be summarized as follows :

• Plasma exchange with fresh frozen plasma was more effective than plasma infusion alone. At six months, the remission rate and survival rate with these two procedures was 78 versus 31 percent (remission) and 78 versus 50 percent (survival) . (The mortality rate is much higher in non responders to these interventions.)

• As noted above, plasma infusion alone is less effective than plasma exchange, and may be complicated by volume overload.

• Plasma infusion without exchange might therefore serve as emergency treatment in those not having immediate access to plasma exchange.

In approximately 15 % of patients, twice daily plasma exchange is required, because of either failure to respond to the initial daily plasma exchange or exacerbation of symptoms.

Twice daily exchange of one plasma volume is more effective replacement therapy than increasing the volume of a single daily exchange. Once recovery begins, single daily plasma exchanges are resumed.

Relapses, defined as recurrent TTP after at least 30 days of no treatment and no evidence of TTP

CASE PRESENTATION

A 37 years old female C/O severe headache, fever, transient weakness & numbness of the left upper limb for 2 days, brought to E.R in confusional state, irritability, then she developed two attacks of convulsion in the recovery room.

Not known to have any chronic medical illness before.

No history of recent travel. Negative drug history.

O/E :Confused, Irritable, Pallor, Tinge of jaundice. Febrile 38.3C After few hours, she desaturated, intubated electively and connected to the ventilator later on.

WBC 15.2 Hgb 7.23 Plt 25000 PT 12 PTT 28.1 INR 1.11 Retic 10% Urea 11 Creat 125.7 T.Bili 52.3 Direct 15.3 Indirect 36.9

LDH 1740 Initial CXR: NormalPlain CT-SCAN Brain : on admission: Normal.

Peripheral Blood Film: showed leucoerythroblastic picture, reticulocytosis, fragmented red cells, severe thrombocytopenia.

Coomb's test (direct, indirect): Negative. Malaria Film X 4: Negative. RF : Negative. ANA: Negative. U/S Abdomen & Pelvis: Mild hepatomegaly only. Bone Marrow Aspiration: Hypercellular bone

marrow with megakaryocytic and erythroid hyperplasia.

Hospital Course:

Patient intubated (electively) on the same day of presentation.

Plasma Exchange requested immediately. FFP transfusion started as a bridge to Plasma Exchange . After two days, She developed Two attacks of

generalized tonic clonic convulsions, Diazepam iv given, Phenytoin started.

She transferred from recovery room to I.C.U bed 12. Within 10 days, her level of consciousness is improved

gradually, became responding to verbal commands. After Two weeks, extubated, shifted to the general ward.

The patient become fully conscious, oriented , alert but we discovered that she is (Quadriplegic). Plasma Exchange stopped.

Plain CT-SCAN Brain repeated: showed multiple small infarctions at RT.parital lobe, RT.frontal lobe and LT.parital lobe.

MRI Brain, Brain stem, Cervical spine done: showed: High signal intense lesions at: Rt.internal capsule, LT.internal capsule Rt.frontal white

matter. Para ventricle lesion(parital lobe). Biparital white matter. Mild focal disc plugging. One day before discharge: WBC 9.6 Hgb 11.2 PLT 519 Urea 4.2 Creat 50 K+ 3.8 LDH 390

Length of hospital stay: 31 days.

TABLE 26/7 25/7 24/7 23/7 22/7 21/7 20/7 19/7 18/7 16/7 15/7 14/7 13/7 12/7 11/7 10/7 LAB

7.9 7.1 6.1 5.9 9.3 7.3 11.0 6.6 8.0 8.1 14.5 15.2 17.8 11.6 15.2 23.6 WBC

10.4 9.5 9.4 9.6 10.6 10.7 10.6 7.1 8.3 8.4 9.9 7.0 8.1 8.15 9.1 8.1 Hgb

472 314 317 229 183 248 113 88 65 49 12 53 42 24.6 27 20 PLT

4.8 5.2 4.7 5.0 4.5 5.8 5.9 5.3 4.7 7.5 8.2 7.1 9.2 12.7 16.8 14.8 Urea

45 35 54 56 63 49 64 81 49 55 67 88 99 116 135 127 Creat

261 344 299 353 350 573 1260 1152 677 1636 2850 1450 LDH

Plasma Exchange: started 07/07 D/C 23/07 TOTAL FFP : 305 units PRBCs transfusion: B +ve

TOTAL PRBCs: 16 units

A Disintegrin-like And Metalloprotease with ThromboSpondin type1)

Schedule and rate of response : Plasma exchanges should be performed daily until the

platelet count and serum (LDH) concentration are normal for two to three consecutive days. On average, 7 to 16 daily exchanges are required to induce remission, but the variability is large and unpredictable, ranging from 3 to 145 required exchanges.

The recommended volume to be exchanged is one estimated plasma volume per procedure.

The following formula can be used to estimate the plasma volume in an adult :

Estimated plasma volume (in liters) = 0.07 x Weight (kg) x (1 -

Hematocrit)

Simply: Estimated plasma volume (in ml) = T. Blood volume x (1 -

Hematocrit) T. Blood volume (in ml)= Female 69 X weight (kg) Male 70 X weight

(kg) For example: Male patient , 70 kg , Hematocrit 20% T. Blood volume (in ml)= 70 X 70 = 4900 ML Estimated plasma volume (in ml) = T. Blood volume x (1 -

Hematocrit) 4900 X ( 1 - 0.20 ) = 3920 ML

Summary TPE plays an important role in the treatment of several

autoimmune, neurological, hematological, renal disorders. TPE is not without risks and hazards (e.g., vascular access,

bleeding, allergy), which should also be considered. Idiopathic familial and nonfamilial thrombotic

thrombocytopenic purpura as well as the subset of the hemolytic uremic syndrome not associated with diarrhea are clear indications for TPE using fresh frozen plasma as replacement fluid.

Patients with myasthenic crisis will also benefit from TPE and will improve within 1 day.

Acute pancreatitis as a complication of the chylomicronemia syndrome has a poor prognosis and should be treated with TPE without any delay.

plasmapheresis in icu

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