This is a disclaimer:
As with all material presented on this site, please use your own judgement as to what you feel is clinically safe, vetted, and makes sense to you.
This blog is NOT peer reviewed or sanctioned by any perfusion associated review board or academic body.
That is not to say that what I put down on this blog is slipshod or otherwise- I take great pride in my work, but recognize the limitations of relying on published information on the internet. As a perfusionist of 23 years, and 30 heart programs later, I think that lends some merit and credibility in terms of siphoning off the wheat from the chaff.
All materials presented are as well researched as possible, are more often than not- from academic sources removed from the internet- thus vetted, and cited appropriately.
You be the judge.
Do I personally trust this material? Absolutely! But ‘Surfers is intended to be a quickly accessed resource, basically get your aim close to the target, and let you decide if what you are reading makes sense and works for you.
so please use common sense and apply this material to what directly relates to you.
Frank Aprile, BBA, LP, CCP
VAD / ECMO Policy
(Written with assistance from Thomas Doyle, MS, CCP)
A board certified/certification eligible perfusionist will be responsible for the set-up, monitoring, and administration of all Ventricular Assist Device (VAD) procedures and/or Extracorporeal Membrane Oxygenation (ECMO) procedures.
Mechanical circulatory assistance may be used when cardiac output from native ventricle(s) is incompatible with life, despite maximal pharmacological and/or IABP support. Support of the systemic circulation reduces the possibility of multi-organ failure by providing blood flow and pressure to vital organs. The use of a VAD also provides a metabolic rest for the heart, therefore, theoretically enabling the myocardium to expend energy to repair itself rather than to support the systemic circulation. With this in mind, the decision to implement the use of a VAD is to provide an artificial bridge to either myocardial recovery or to cardiac transplantation.
Ventricular Assist devices are used on an as needed emergency basis, therefore, scheduling is dependent upon surgeon’s request.
IV. PATIENT SELECTION:
1. Inability, to wean from CPB, after technically successful cardiac surgery. This may be due to left and/or right ventricular failure.
2. Continued ventricular power failure in spite of conventional treatments such as: volume loading, pharmacological therapy, and IABP.
3. Inability to use IABP and/or IABP unable to adequately augment the ventricle.
4. Sustained recurrent malignant dysrythmias.
5. Development of low cardiac output syndrome within 72 hours of a technically successful cardiac surgery.
6. Acute lung failure.
7. Age less than 70 years.
1. Age greater than 70 years.
2. Brain death.
3. Blood dyscrasia.
4. ARDS > seven days.
5. Surgery technically unsuccessful.
6. COPD / Emphysema
7. Organ dysfunction – chronic renal failure, hepatic dysfunction.
9. Bacterial Endocarditis
10. Unfavorable anatomical findings.
C. Criteria for Patient Selection:
1. Cardiac Index < 1.8 L/min/m2 in Adults
2. Mean Arterial Pressure < 60 mmHg
3. Left or right atrial pressure > 20 mmHg
(For isolated RV failure, the above finding with a LAP < 12 mmHg)
4. Urine output < 20 ml per hour.
5. Arterial PO2 < 60 mmHg with adequate cardiac index > 2 L/min/m2 for ECMO.
(The above criteria may be present in spite of optimal inotropic and vasodilatating drug support.)
If a VAD is indicated based on the above selection criteria, VAD insertion should proceed as soon as possible. Prolonged hesitation may lead to multi-system failure.
V. DETERMINATION OF FAILURE MODE:
A. Pure myocardial failure may be from:
1. Isolated LV or RV dysfunction or both
2. May require LVAD, RVAD, combined LVAD/RVAD (BIVAD)
3. May have associated lung failure, may require the use of an oxygenator, ECMO
B. Isolated RV Failure:
1. Deemed present when CPB cannot be discontinued due to inadequate LV filling (pre-load) by the RV output. RV contractility is depressed, CVP elevated, systemic cardiac output depressed, and LAP, if elevate, is lower than the RAP. Mechanical dysfunction of the RV (pulmonary emboli, tricuspid regurgitation, reversible RV ischemia, or pulmonary vasospasm) must be eliminated.
NOTE: It is essential to have a CVP monitoring line a Swan-Ganz thermodilution catheter (preferably with SVO2 capability), and a left atrial monitoring line in place to continuously monitor cardiac output and the filling pressures of both the left and right ventricles.
2. A trial of RV support can be accomplished by the following methods:
a. Cannulate the pulmonary artery with a 20 Fr. femoral artery cannula (USCI, RMI, etc.).
b. Convert total CPB to RA–>PA bypass by discontinuing total CPB. Remove tubing from aortic cannula and reattach it to the PA cannula.
c. Gradually reinstitute bypass and assess the cardiac and pulmonary function. If the CVP decreases and the LAP increases with an improvement in cardiac output, the RV failure is present and the right ventricle can be successfully augmented using an RVAD. In this mode, oxygenated blood is being delivered to the PA. Since pulmonary failure is a potential mechanism for right heart failure, the ability of the lungs to oxygenate is tested by reducing the FiO2 to the membrane oxygenator and observing the PAO2. (Anesthesia should be fully ventilating at this time.) Low PAO2 present prior to the institution of RV assist may improve despite the persistence of an intra-pulmonary AV shunt. This occurs because the increased cardiac output diminishes the AVO2 difference which very favorably affects arterial O2 sats.
d. If an improvement in blood pressure and cardiac output is not observed after the LAP increases, then biventricular failure may exist. At this point, consider IABP and or LVAD to assist the left ventricular function.
e. Pulmonary function is further tested by observing changes in lung compliance and the amount of pulmonary secretions. If oxygenation is unsatisfactory, ECMO should be considered. During the early perioperative period, use of an oxygenator with the anticoagulation is associated with severe bleeding problems which can be fatal.
C. Isolated LV Failure:
1. Deemed present if unable to discontinue CPB due to poor LV function, elevated LA pressure, and decreased cardiac output associated with arterial hypotension. Mechanical (correctable) ventricular dysfunction (LV outflow obstruction, severe mitral regurgitation, mitral stenosis, aortic insufficiency, vasospasm, or prosthetic malfunction) must not be eliminated.
NOTE: It is essential to have a CVP monitoring line a Swan-Ganz thermodilution catheter (preferably with SVO2 capability), and a left atrial monitoring line in place to continuously monitor cardiac output and the filling pressures of both the left and right ventricles.
2. Atrial support of LV support can be accomplished by the following methods:
a. Cannulate the left atrium with a wire reinforced venous cannula. Caution must be taken not to introduce air into the left atrium during cannulation. This may be accomplished by inflating the lungs, filling the pericardium with saline, and insuring the LA pressure is > 10 mmHg.
b. Convert CPB to temporary LVAD (LA–>Ao) by discontinuing total CPB briefly. The systemic venous return cannula is clamped and disconnected. The venous line is then reattached to the left atrial cannula.
c. Gradually reinstitute bypass and assess the cardiac function. If the LA pressure decreases and arterial blood pressure improves with the flow from the pump, then prepare the LVAD system. Total CPB is reinstituted and the LVAD is inserted. Prior to inserting the LVAD, any patent foramen ovale should be closed. The high RAP and low LAP often associated with LVAD support, can produce a right–>left shunt with profound hypoxemia. If patient is hypoxemic on LVAD and pulmonary oxygen saturation’s are normal, a right to left shunt is easily ruled out with a Doppler study.
d. If the temporary LVAD is unable to generate an adequate blood flow rate, then on should suspect catheter entrapment, hypovolemia, or RV failure (CVP > 20 mmHg. Biventricular failure may exist and BIVAD should be considered (30%) incidence. During LVAD support, the RV output determines the entire cardiac output because it supplies blood to the LA and, in turn, to the LVAD. RV may need inotropic support. If marginal RV failure is present (manifested by low LVAD output), and RVAD should be used to augment RV function. This is especially true if the pulmonary vascular resistance might later become elevated. This can occur with multi-system failure, as is seen with multiple blood transfusions and sepsis.
A. General Information:
Right VAD cannulation utilizes the RA for pump inflow and the mainstream PA for return flow. Similarly, left VAD cannulation utilizes the LA and aortic root for vascular access. Placement of the inflow cannula in the atrium proper is particularly important: blood flow into the cannula must not be impeded and the cannula itself should not mechanically interfere with the tricuspid or mitral valve function.
Special care should be used in selection of cannula size and design. Internal diameters should be sufficient to maintain cardiac index (CI) up 2.2-2.4 L/min/m2. Inflow cannulae should be a minimum of 4-6 Fr. sizes larger than outflow cannulae. Without the use of an external venous reservoir, the negative pressure provided by the pump “suction” directly on the atrial cavity minimizes the flow limitation characteristic of small cannula drained by gravity. It has been shown however, that a higher hemolysis rate does occur when blood is exposed to negative pressure than when it is exposed to comparable absolute values of positive pressure. As the cannulae must be externalized through an approximated sternotomy incision, wire-wound cannulae should be considered to minimize kinking.
B. Cannulae Placement:
1. The surgeon is responsible for cannulae placement. RA is usually cannulated through the right atrial appendage. LA is usually cannulated through the right superior pulmonary vein. PA is directly in the main PA. Ao is usually accomplished by using the same cannula that was used during the CPB procedure.
2. Each cannula is surrounded by a simple 2-0 purse string suture and secured in place by the use of a “keeper” or tourniquet kit.
3. All cannulae must be externalized through either an approximated sternotomy incision or through an intercostal incision.
4. A meticulous attempt must be made at hemostasis prior to leaving the operating room. Fibrin glue (Ca++, thrombin and Cryoprecipitate) can be helpful.
5. It is imperative that atrial cannulae do not interfere with their underlying valve structures.
6. Likewise, it is imperative that a PA catheter, if use, does not interfere with the native pulmonary valve or provide unilateral lung hyperperfuison.
C. Cannulae Selection:
The largest and shortest single stage cannula should be used to reduce resistance and hemolysis.
1. PA or Ao CANNULATION:
14 Fr. – < 1 L/min VAD flow
16 Fr. – < 2 L/min VAD flow
18 Fr. – < 3 L/min VAD flow
20 Fr. – < 4.5 L/min VAD flow
24 Fr. – < 6.5 L/min VAD flow
2. RA or LA CANNULATION:
30 Fr. – < 3.0 L/min VAD flow
32 Fr. – < 4.5 L/min VAD flow
34 Fr. – < 6.5 L/min VAD flow
** Wire reinforced cannula with a light house tip is preferred to minimize the risk of catheter entrapment and kinking.
1. Heparin Bonded VAD Pack
2. Cannulae (arterial/venous)
3. If ECMO, Membrane oxygenator with integral heat exchanger and holder.
4. Disposable pump head
5. Flow transducer
6. Disposable flow probe
7. Balanced electrolyte solution (minimum of 3-1 liter bags).
8. Heparin (access to NaHCO3, Mannitol, and CaCl2 is advised).
9. Perfusion flow sheet/pump record/VAD flow sheet.
10. Hemoconcentrator and tubing set.
11. 2 each – 3/8 x 3/8 LL connectors.
12. 2 each – 3-4 way stopcocks.
13. If used, 1 cardiotomy.
14. If used, 1 rapid prime line.
B. Capital Equipment:
1. Centrifugal pump console w/ external drive motor, internal battery, and charger.
2. If ECMO, Heater/cooler.
3. ACT machine / Anticoagulation Monitor and tubes or supplies.
4. If ECMO, O2 cylinder.
5. Tubing clamps (minimum of 6 each).
6. Mobile cart with blender / IV pole / power supply.
VIII. PERFUSION RESPONSIBILITIES:
A. A perfusionist is responsible for setting up the system,
sizing cannulae, and to perform or assure the iso-volumetric connection of the system to the patient. The perfusionist will provide 24 hour surveillance and management of the VAD and maintain proper flow, pressure, hemodynamic stability, and anticoagulation.
B. Set-up and Priming:
1. The Universal CPS/VAD pack will be assembled in the VAD configuration utilizing sterile technique. All components and packaging must be inspected for defects to assure sterility and proper function. Expiration should be verified due to the Carmeda coating which has a limited shelf life.
2. If hemoconcentration is to be utilized, be sure you place a 3/8” LL connector in both the inlet and outlet tubing of the centrifugal pump head. These connectors should have stopcocks place with AIR-TIGHT caps on all ports. The connectors should be approximately 12” from the inlet and outlet of the pump head.
3. If performing a RVAD and dialysis is to be utilized, place both connectors with stopcocks on the outlet tubing (positive pressure side of the pump), to prevent air embolism.
4. The prime solution will consist of a balanced electrolyte solution. Packaging and expiration dates must be checked to assure sterility.
5. Carefully prime the system (slowly) by institutional protocol. A slow gravity fill is one way to prevent having bubbles in the system.
6. Recirculate the prime to make sure that all bubbles are removed by the recirculation loop established in the bag used for priming.
7. Connect the flow transducer to the flow probe at this time.
8. Clamp both sides of the flow probe and balance (zero and gain) the flow transducer.
9. Once the system is debubbled, primed, and recirculated, you have 4 choices available to you.
a. Remove the priming Y and replace with a 3/8 x 3/8 LL connector with sampling line.
b. Remove the priming Y and replace with a 3/8” straight connector.
c. Leave the double spiked priming Y for volume additions. Each line must be double clamped at all times that volume additions are not being made.
d. Replace the spike on the prime line closest to the pump head with a 1/4 x 3/8 straight connector. Attach a 4-6” piece of 3/8 x 3/32” tubing to the connector and the other end to the bottom of a cardiotomy (from your shelf stock) and double clamp below the cardiotomy. Attach a rapid prime line to the top of the cardiotomy. This set-up provides you with an excellent source for volume additions such as: PRBC’s, FFP, electrolyte solution, Albumin, cell saver blood, etc.. NEVER allow the volume in the reservoir to go below the 100cc level. Always keep outlet to cardiotomy double clamped unless making volume additions.
10. To prepare for cannulation, the mobile cart must be pushed up to the table. The pump turned off and both the inlet and the outlet of the pump head clamped.
C. Anticoagulation Management:
1. After the patient is place on the VAD – if the patient is systemically anticoagulated at the end of CPB, the protamine dose is calculated as per normal protocol and the heparin is totally reversed.
2. Once hemostasis has occurred, generally 3-4 hours post protamine, in the absence of a heparin bonded circuit or in the face of flows less than 2.0 L/min, a heparin infusion is begun to maintain ACT’s between 170-200 seconds. Initial heparin infusion should be calculated at 40u/kg/hr and monitored frequently as metabolism lowers the level of circulating heparin. Example, a 90 kg man would require 3600u/hr. Mix 20,000u of heparin in a 250 ml bag of 5% dextrose = 80 u/ml. Infuse at 45 ml/hr with a IV infusor pump.
3. Initially, ACT’s are measured every half hour until anticoagulation has stabilized and then every hour during VAD support.
4. If platelets are administered, then the ACT should be performed post-infusion since their administration may shorten the ACT.
5. If FFP is administered, an ACT should be performed due to its tendency to lengthen the ACT (because of its Antithrombin III content).
6. Other situations which mandate more frequent ACT monitoring include diureses, hemoconcentrator usage, and dialysis.
7. As VAD flow is decreased below 1.5 L/min., the heparin infusion is increased to maintain ACT’s between 220-250 seconds. If an interruption in flow is anticipated, as in the changing of pump head, ACT’s are increased to 360 seconds prior to interrupting flow.
8. Should VAD be required electively due to progressive myocardial deterioration, 1.0 – 1.5 mg/kg dose of heparin should be administered IV push at least 10 minutes prior to anticipated cannulation. This will allow thorough distribution in the sluggishly circulating blood volume.
9. Blood flow should always be maintained greater than 750 ml/min. regardless of anticoagulation.
D. VAD Initiation:
1. During connection of the cannulae, it is important that both inflow and outflow tubing is clamped to reduce the possibility of additional negative pull on the inflow portion of the pump.
2. After cannulae are connected, remove the clamp from the inflow tubing (RA or LA cannula lines) and increase RPM’s on the pump console to approximately 1800-2000.
3. Remove the clamp from the pump head outlet and gradually increase the RPM’s and flow thus slowly taking over the work load of the ventricle(s) you are supporting.
4. Flow must adequate to support > 2.2 L/min/m2 of flow. If not, determine if the following are causing the problem: hypovolemia, height gradient, problem with pre-load (often a problem in LVAD when the RV performance is marginal).
5. Communication with the surgeon and anesthesiologist is vital at this point. Noise in the room should be kept to a minimum.
6. Continue to increase flow gradually while maintaining a CVP or LA pressure depending on RVAD or LVAD at no less than 10 and not more than 15.
E. VAD Management:
1. Flow is regulated to maintain adequate filling pressures (>10, <20) and adequate systemic blood pressure.
2. Inotropic support is decreased or discontinued to decrease the myocardial oxygen consumption.
3. SVO2 should be monitored (preferably by Swan Ganz) and flow adjusted to keep SVO2 between 70-75%. In the absence of a Oxymetric Swan, a Saturation or Sat/Hct probe may be place in the venous line for continuous monitoring. You may decide to place a CDI or like probe and sensor in the venous line for continual VBG monitoring.
4. If bleeding is not a problem, coagulation abnormalities are not aggressively corrected until the patient is to be weaned. If chest tube drainage is excessive, the cause and source of bleeding should be determined. This may require surgical exploration in the ICU.
5. Platelets are administered to maintain a platelet count >75-100,000. FFP and cryoprecipitate may be administered for factor deficiencies or a fibrinogen level < 150 mg/dl.
6. Hematocrit should be maintained > 30%, 35 – 40 % is preferred.
7. The following laboratory tests are routine for VAD support:
(a) Platelet counts, hematocrit, fibrinogen, Albumin, electrolytes a minimum/q4 hrs.
(b) BUN and Creatinine /q 12 hrs.
(c) Blood and urine cultures, plasma hemoglobin, fibrin split products, and cardiac enzymes /q day.
8. A hemoconcentrator may be useful if the patient is hypervolemic, hemodiluted, or if marginal renal failure exists. The hemoconcentrators inflow line is attached to the outflow or high pressure line of the VAD by connecting it to the previously inserted stopcock on the 3/8 x 3/8 LL connector. The hemoconcentrators outflow line is connected to the inflow line of the VAD by connecting it to the previously inserted stopcock on the 3/8 x 3/8 LL connector. Care must be taken to insure that all air has been removed from the hemoconcentrator during priming of the unit. This procedure may be hazardous during LVAD due to the possibility of introducing air. Always attach the effluent to and occlusive IV pump to regulate the volume removed or to a regulated vacuum source for volume removal.
9. Use of the hemoconcentrator during RVAD may not be successful due to the low pressure on the VAD outflow line. Often, a driving pressure of at least 100 mmHg is necessary for the hemoconcentrator.
10. If dialysis is required the same connections as for the hemoconcentrator can be made or if RVAD was known in advance, your connectors should both be placed on the outlet (positive pressure) side.
11. A second pump head, a battery pack, and a hand crank should be in close proximity to the patient. If the pump stops, and AV fistula is created since the pumps are non-occlusive
12. The pump should always be operated in the RPM mode and not the auto flow mode (if it is available).
13. A perfusionist is required to be in attendance at all times to monitor, maintain, and troubleshoot the VAD system in order to optimize patient care and safety.
14. Entries on the VAD flow sheet are a minimum of every 30 minutes or more frequently if alterations are made. Entries include the following:
(a) Blood pressure, CVP, LA, VAD flow, VAD RPM’s, venous or arterial saturation, heparin dosage (if any), ACT’s, chest tube output, urine output, blood gases, hematocrit, calculated cardiac output, other lab results, pharmacological support, blood, fluid platelets, FFP, or cryoprecipitate administered.
15. During LVAD support, once each 30-60 minutes (regular intervals), the VAD flow is briefly decreased to allow an increase in blood flow through the failing ventricle. This is call s “sigh” for the ventricle. If the ventricle is contracting, this maneuver may prevent long term stasis of blood in the ventricle and reduce the possibility of thrombus formation.
16. Patients may be transferred from the O.R. to the ICU by utilizing the pump console battery pack or hand crank.
** Remember, any time there is a failure in VAD flow that you cannot correct quickly or by handcranking, in the absence of adequate ejection, it should be considered as an arrest and treated as such until such time as VAD flow can be restored.
17. Upon successful transportation of the patient and VAD to the ICU, immediately plug the pump console into an outlet with emergency power capabilities.
18. The wheels of the mobile cart should ALL be locked in place for security and patient safety.
19. Patients in the ICU should be placed in reverse isolation. It may be advisable to choose antibiotic therapy which is sensitive to the predominate ICU organism.
20. The chest is generally closed. However, if hemodynamics deteriorate, the chest is left open and dressed in sponges soaked in Betadine and covered with an adhesive plastic drape. Chest tube drainage should not be reinfused to the patient due to possible contamination if the chest has been left open. The chest closure must be air tight to prevent room air from being aspirated through the wound into the chest tubes, thereby mediastinal contamination.
F. Weaning Procedure:
1. Before initiation of weaning protocols, a specified period of strict recovery should be allowed where filling pressures and inotropic support should be kept at nominal values and VAD flows are maximized. This period may be as brief as 2-4 hours for RVAD because of the inherently lower RV workload, but should be no less than 12-24 hours for LVAD. If initial weaning is unsuccessful, another 24 hour “rest” should be provided to the ventricle.
2. Weaning is achieved by slightly decreasing the pump output by 500cc increments each hour for several hours. The filling reassure should be observed carefully following flow reduction. Ideally, filling pressure should not increase and greater ventricular ejection should occur. A slight elevation and plateauing filling pressure with differential ventricular response may best be responded to with increased inotropic support while maintaining pump flow at its lowered level. Steadily increasing filling pressures with little observable ventricular response should result in returning pump flow to its previous level and either allowing a period of ventricular rest, with or without elevation of inotropic support.
3. Once the failing ventricle appears to be recovered, the heparin infusion is increased to extend ACT’s to the levels described under anticoagulation management.
4. Each successful step in the weaning process should be followed by another decrease in VAD flow. Unsuccessful steps should be followed by a period of myocardial rest at the last successful flow. Decreases in flow achieved only with significant inotropic increases should result in a greater time increment between weaning steps. Caution must be applied when evidence of myocardial ischemia or cardiac insufficiency is observed, i.e. arrhythmia’s, EKG changes, systemic acidosis, etc..
5. When absolute pump flow reaches 1 L/min/m2 in adults, preparations may be made to return the patient to the O.R. for removal of the VAD and chest closure. Should the surgeon decide to remove the VAD in the ICU, everything necessary to re-initiate the VAD should be on hand at the bedside. Abrupt cessation of VAD support from the above listed flows may not be easily tolerated, so it may be advisable to make a few small decreases during the last few minutes prior to draping the patient for the removal procedure. Routinely, a trans-thoracic ECHO or TEE will be performed to evaluate the ventricular function prior to and during discontinuation of the VAD. If hemodynamic alterations are not within acceptable range, adjustments to pharmacological support or short extension of VAD support may be indicated. Some slight level of VAD flow must be maintained until the very moment of decannulation.
6. When a successful weaning procedure has been concluded, clamp both inlet and outlet lines and turn off pump console.
7. The patient should be observed carefully to ensure hemodynamic stability: re-cannulation may be required if the patients condition deteriorates and is unresponsive to drug therapy. If the patient remains stable, every effort necessary to return anticoagulation level to normal must be made, and the patient returns to the normal post-open heart recovery phase.
G. Bi-Ventricular Support:
1. Simultaneous LVAD and RVAD is sometimes necessary and adds another level of complexity to patient management. A helpful suggestion is to treat the left ventricle first and react to right-sided changes if they occur.
2. It can be anticipated that the right side will recover before the left, and thus the RVAD weaning may be completed long before LVAD weaning has progressed very far, if at all.
3. In this instance, RVAD flow should be maintained at 1.0-1.5 L/min/m2 to prevent stasis until LVAD weaning is successful and bilateral de-cannulation is possible.
H. Clean-up Procedure:
1. The VAD system should be torn down, the disposables properly bagged and labeled as a bio-hazard.
2. The pump console and the mobile cart should then be terminally cleaned with an approved germicide. (See Infection Control)
3. The mobile cart should then be restocked with the appropriate items.
A. Sample & Considerations for: Physician VAD Orders:
1. Maintain blood flow at approx. _________L/min.
2. To maintain flow administer _____________________ if Hgb/HCT % is
less than _________ and _________________________ if Hgb/HCT % is more than ______.
3. Arterial pressure should be maintained at approx. _______mm Hg.
4. CVP should be maintained at approx. _____ mm Hg using #2 above.
5. LAP should be maintained at approx. ______mm Hg using #2 above.
6. The heparin drip of 20,000 units of heparin in 250cc of 5 % dextrose should be given at a rate of ________ to maintain a
minimum ACT of _______ and/or PTT of _______.
7. _______Units of platelets should be given when platelet count is less than ___________.
8. _______Units of cryoprecipitate should be given when fibrinogen level is less than __________.