transfusion medicine anticoagulation therapeutics perioperative medicine critical care choosing...

Update in Hospital Medicine 2013

Thomas Frederickson, MD, FACP, SFHM, MBAMedical Director, Hospital Medicine

Alegent Creighton Health

Topics

Transfusion Medicine Anticoagulation Therapeutics Perioperative Medicine Critical Care Choosing Wisely


Case 1

CC: dizzy and black stoolsHPI: M.S. is an 78 yo female with 2 day history of 6 black, foul smelling sticky stools, and one day history of mild dizziness, fatigue, DOE and nausea. No vomiting or syncope. PHM: HTN, DMII, a-fib, OAPSH: Cholecystectomy, TKA on RMeds: Diltiazem, Lisinopril, Metformin, Warfarin, Acetaminophen, PRN Ibuprofen about twice per week


Case 1cont.

SH: lives alone, independent in ADLs, widowed, non smoker and non drinkerFH: CAD in father who died at 64, son with CAD post CABGROS: otherwise neg, no abd pain, no CPPE: Gen – NAD, 128/74, 14, 108, 36.6, wt 56 kgENT – scleral pallorCV – Irregular, no Murmur


Case 1cont.

Pulm – CTA, non laboredAbd – NABS, no masses, mild mid-epigastric tenderness without G/R tendernessExt – no C/C/ENuero – non-focal, A&OX3Labs – INR 3.6, PTT 31.1, Hb 6.7, HCT 20.1, BS 187, rest of CBC and CMP WNL


Case 1cont.

ED Course – 3 units FFP, 2 units RBC, I L NS, transfer to ICU, 2 16 gauge IV were placed, GI consult, Pantoprazole bolus and drip ordered, EGD scheduled for the following morning, H/H every 6 hoursUpdate 10 hours later – One more episode of melena, no N/V, repeat Hb 7.7, VSS, HR 89


Question 1

What is you RBC transfusion strategy for this patient?A. Transfuse 2 units RBC now, cont Q6 hr

H/H, transfuse to a Hb target >9B. Transfuse 1 units RBC now, cont Q6 hr

H/H, transfuse to a Hb target >9C. Cont Q6 hr H/H, hold transfusion for

now, transfuse to a Hb target >7D. GI is on board, let them worry about it!


Transfusion Strategies for Acute Upper Gastrointestinal BleedingNEJM, 2013 Jan;368(1):11-21

Objective – compare restrictive vs liberal transfusion strategy in UGIB

921 patient with UGIB randomized to liberal (Hb target >10) or restrictive (Hb >7) transfusion strategy

Exclusions – LGIB, exsanguination, shock, active coronary syndrome

Endpoint – 6 week mortality Results – survival in restrictive 95% vs 91 % for liberal

(.55 HR, CI .33-.92, p=.02) Also advantage for restrictive in re-bleeding 10% vs

16%, p.01) Take home – better outcomes in UGI bleed with

restrictive strategy, even in variceal bleedingUpdate in Hospital Medicine 2013

Case 1cont.

Further course – The patient remained stable, no further melena. She received no further blood products. EGD showed a GU with a clean base and no active bleeding, clot or visible vessel. On hospital day three the patient was discharged to home on her home medications except warfarin and ibuprofen. Pantoprazole 40 mg daily was added


Question 2

When should Warfarin be restarted?A. In one monthB. In 2 weeksC. In 4 daysD. Never – are you crazy!!


Risk of thromboembolism, recurrent hemorrhage, and death after warfarin therapy interruption for gastrointestinal tract bleeding. Arch Intern Med. 2012;172:1484-9

Retrospective cohort study GIB – 219 restart Warfarin in less than 2 weeks, 180

did not restart within 2 weeks Restart Warfarin –

› Mean time 4 days (IQR 2-9 days)› Thromboembolism HR .05 ( CI .01 - .58)› Death .31 (.15 - .62)› GIB 1.32 ( .5-3.57)

Restart group - 0 thromboembolic events Not restart group – 11 thromboembolic events,

including 3 deaths from CVA Take home – restart Warfarin after GIB


Case 1cont. One year later

M.S., now 79 and has worsening L shoulder pain form OA. She was medically evaluated by her PCP prior to an elective L total shoulder arthroplasty. You are consulted in the hospital to manage her anticoagulation. Her exam and medications are unchanged. Her 5 mg per day dose of Warfarin was discontinued 5 days pre-op. Her post op Hb is 11.8, Cr. 0.5 and INR is 1.0


Question 3How would you manage her anticoagulation?A. Enoxaparin 1.5 mg/kg sub-q starting

POD#1 and restart Warfarin POD 0B. Enoxaparin 1.5 mg/kg sub-q starting

POD#2 and restart Warfarin POD 0C. Enoxaparin 40 mg sub-q starting POD

0 and restart Warfarin POD 0D. SCDs starting POD 0 and Warfarin

starting POD 0Update in Hospital Medicine 2013

Predictors of major bleeding in peri-procedural anticoagulation management. J Thromb Haemost. 2012;10:261-7.

Cohort study 2,182 patients on long term Warfarin Study peri-procedural bleeding associated with LMWH

bridging 1496 received bridging, 686 did not 5.1% bleeding, 2.1%major bleeding Bridge - 3% major, no bridge -1% major (p=.017) Major bleeding – Bridging <24 hr post op (HR 1.9, CI

1.6 – 3.4) No major bleeding <24 hr if not on LMWH Authors conclusions: bridge only high risk and at 48hr Cautions – study groups had different characteristics


Case 2

CC: can’t walkHPI: S.M is an 72 yo R handed male with a 7 hour history of difficulty walking. He had difficulty getting up from the kitchen table and had to hold on to furniture because of falling to the R. He had difficulty trying to dial his daughter’s PN. When his daughter arrived on her way home from work she noticed slurred speech and called 911PHM: COPD, HTN, DM2, hospitalized one time in the past year for AE-COPDPSH: appendectomyMeds: fluticasone/salmeterol, tiotropium, albuterol, amlodipine, metformin, glimepiride


Case 2 cont.

SH: spokes ½ PPD, 50 pack year smoking history, 2 beers/day, lives with daughter, independent in ADLs, divorcedFH: NCROS: no F/C, cough with yellow sputum, no CP, DOE for past 2 days at 30 feet, neuro as above, otherwise negPE: labored breathing and anxious


Case 2 cont.

VS: 149/92, 88, 24, 36.8, O2 sat 91% RAENT: slightly dry oropharynxCard: Regular but distant S1S2 w/o murmurPulm: mildly labored with expiratory wheezing with prolonged expiration Abd: NABS, soft, NT, no massesExt: no C/C, trace pretibial edema


Case 2 cont.

Neuro:A&OX3, mildly slurred speech without word finding difficultly, no gross sensory deficits, diminished strength and coordination in the RUE and RLE, 2+ DTR patellar bilaterally, absent Achilles DTR bilaterallyLabs: CPC, CMP, coags all normal except BS 204CXR: Hyperinflation, no acute infiltrate


Case 2 cont.

EKG: NSR, RAFBHead CT: age appropriate atrophy onlyED course: after passing a bedside swallow eval the patient was given ASA 325 mg po, methylprednisolone 60 mg IV, Levofloxacin 750 mg IV and admitted on your service to the stroke unit on a stroke protocol with a diagnosis of AE-COPD and ischemic CVA


Question 4

What is appropriate anti-plate therapy for therapy patent?A. ASA 325 pm PO dailyB. Clopridogrel 75 mg po dailyC. ASA 81 mg po daily plus

Clopridogrel 75 mg po dailyD. Consult neuro, they will know what

to do


Risk–Benefit Profile of Long-Term Dual- Versus Single-Antiplatelet Therapy Among Patients With Ischemic Stroke A Systematic Review and Meta-analysis Ann Intern Med. 2013;159:463-470.

7 trails, 39,574 patients, index CVA or TIA Recurrent CVA –

› Dual vs ASA OR .89 (CI .78-1.01)› Dual vs Clopidogril 1.01 (.93-1.08)

ICH – › Dual vs ASA.99 (.70-1.42)› Dual vs Clopidogrel 1.49 (1.17-1.82)

Conclusion – dual therapy is not better at preventing CVA, but is more likely to be associated with ICH than Clopidogrel mono-therapy


Case 2 cont.

Hospital course: The patient’s neuro deficits remained unchanged. He was continued on 325 mg ASA daily. He was initiated on levofloxacin 750 mg po daily to be continued for a total of 7 days and prednisone 40 mg daily. His wheezing and subjective dyspnea improved. His BS on his home medications plus SS sort acting insulin were below 180 and above 100. On day three he is being discharged to acute rehab.


Question 5

What is the appropriate duration for the patients prednisone therapy?A. 21 day taperB. 14 daysC. 5 daysD. Let the rehab doc decide


REDUCE JAMA. 2013;390(21):2223-2231

Short-term vs. conventional glucocorticoid therapy in AE-COPD

Randomized, placebo-controlled, double-blinded, non-inferiority

314 patients in ED (92% admitted) with severe COPD (mean FEV1-31%) and AE-COPD, randomized to 5 or 14 day course of 40mg/day of prednisone

No difference in repeat exacerbation at 6 month (5 days=36%, 14 days =37%)

No difference in median time to next exacerbation (5 days pred=45 days until next exacerbation, 14 days =29 days)

No difference in secondary endpoints: death, LOS, hyperglycemia, FEV1, dyspnea index

Conclusion: Short course prednisone non-inferior to long course in AE-COPD Update in Hospital Medicine 2013

Question 6

What are potential complications of this patient’s therapy with levofloxacin

A. Peripheral neuropathyB. Tendon damageC. HyperglycemiaD. Hypoglycemia


Risk of severe dysglycemia among diabetic patients receiving levofloxacin, ciprofloxacin, or moxifloxacin in Taiwan Clin Infect Dis. 2013 Published on line Aug 15, 2013

Population based study, 78,433 patients, floroquinolones, macrolides and cephalosporins

Severe hyperglycemia vs macrolides (per 1,000 patients)› Moxifloxacin (6.9 vs 1.6)› Levofloxacin (3.9)› Ciprofloxacin (4.0)

Severe hypoglycemia vs macrolides (per 1,000 patients)› Moxifloxacin (10 vs 3.7)› Levofloxacin (9.3)› Ciprofloxacin (7.8)

Diabetics using oral fluoroquinolones faced greater risk of severe dysglycemia.


FDA requires label changes to warn of risk for possibly permanent nerve damage from antibacterial fluoroquinolone drugs taken by mouth or by injection. http://www.fda.gov/downloads/Drugs/DrugSafety/UCM365078.pdf

FDA required a label changes to warn of risk for possibly permanent nerve damage

Previously was part of package insert only IV and oral Can be permanent and disabling Onset can be in as little as three days FDA reporting system cannot calculate risk Known since 2004


Case 3CC: I’ve fallen and I can’t get upHPI: T.F. is an 86 yo female who fell while getting back into bed. She tripped over the upturned corner of a throw rug. She is experiencing pain in the L groin that radiates down the anterior aspect of her upper leg. She could not get up but was able to crawl to her phone and call for help. She has no other injuries or pain and no syncope. She had one previous fall 2 years ago.PHM: HTN, DMII, OA, macular degeneration, CAD post CABG in 1991, echo 18 mo ago with no WM abnormalities or significant valvular disease, grade 1 diastolic dysfunction PSH: CABG, TKA on RMeds: Metoprolol, Lisinopril, HCTZ, Metformin, ASA, Acetaminophen, Simvastatin


Case 3 cont.

SH: 20 pack year smoking history, quit in 1991, no EtOH, lives in assisted living, walks with a walker, widowedFH: NCROS: no CP with exertion or at rest, no DOE, palpitations, orthopnea, PND, pedal edema, otherwise neg, BS usually <150, checks one time dailyPE: resting comfortably in ED after 2mg IV morphine


Case 3 cont.

VS: 108/62, 66, 14, 36.4, O2 sat 97% RAHead and Neck: NC/AT, neck non tender CV: Regular S1S2 w/o murmur, bilateral palpable DP and AT pulsesPulm: CTA, non-laboredAbd: NABS, soft, NT, no massesMS: externally rotated L foot, shortened L legExt: no C/C/E


Case 3 cont.

Neuro:A&OX3Labs: CPC, CMP, coags all normal except BS 159, Troponin < 0.04EKG: Inferior Q waves seen on previous EKG, SRL Hip x-ray: L non-displaced femoral neck fractureHospital Course: The patient is admitted to you and you consult ortho. You let ortho and anesthesia know that she is a low to moderate risk for peri-operative cardiac complications and to proceed with surgery without further testing.


Question 7

What is your plan for post operative cardiac surveillance?

A. NoneB. Telemetry monitoringC. Telemetry monitoring and serial

troponinsD. Consult cardiology, they will know

what to doUpdate in Hospital Medicine 2013

Clinical presentation and outcome of perioperative myocardial infarction in the very elderly following hip fracture surgery. J Hosp Med. 2012;7:713-6.

Case control (2:1), retrospective study, 1,212 hip fx patient cohort, median age 85

169 with MI (14%), 92% in <48 hr post-op, 75% “silent”

Mortality MI vs no-MI-› In hospital 14.5% vs 1.2%› 30 day 17.4% vs 4.2%› 1 year 39.5% vs 23%

Limitations: 1998-02, limited use of b-blocker, statin and ACE-I

Conclusion – consider cardiac surveillance in elderly hip fx patients


Risk factors for unplanned transfer to intensive care within 24 hours of admission from the emergency department. J Hosp Med. 2013;8:13-9

Describe risk factors for unplanned ICU transfer within 24 hours of ward arrival from the ED

178,315 ED to floor admissions At risk for ICU transfer <24 hr:

› PN (OR 1.5, CI 1.2 – 1.9)› MI (1.5, 1.2 – 2.0)› Sepsis (2.5, 1.9 – 3.3)› COPD (1.4, 1.1-1.9)› Night admissions, male sex

Decreased odds - high volume ED, admissions to monitored transitional care

Conclusion – Respiratory conditions, MI and Sepsis should be triaged objectively out of the ED


Choosing Wisely

Medical specialty societies were asked to “choose wisely” and identify five tests or procedures commonly used in their field, whose necessity should be questioned and discussed

Sponsorship - ABIM Foundation Partnership with Consumer Reports to

develop and disseminate patient-friendly materials


Choosing Wisely

Aims - promote conversations between physicians and patients by helping patients choose care that is:› Supported by evidence › Not duplicative of other tests or

procedures already received › Free from harm › Truly necessary


Choosing Wisely - Adult Hospital Medicine

Don’t place, or leave in place, urinary catheters for incontinence or convenience or monitoring of output for non-critically ill patients (acceptable indications: critical illness, obstruction, hospice, perioperatively for <2 days for urologic procedures; use weights instead to monitor diuresis).



Don’t prescribe medications for stress ulcer prophylaxis to medical inpatients unless at high risk for GI complications.

Avoid transfusions of red blood cells for arbitrary hemoglobin or hematocrit thresholds and in the absence of symptoms of active coronary disease, heart failure or stroke.



Don’t order continuous telemetry monitoring outside of the ICU without using a protocol that governs continuation.

Don’t perform repetitive CBC and chemistry testing in the face of clinical and lab stability.


Summary

In UGIB use a transfusion threshold in most patients of 7 mg/dl

Consider resuming appropriate anticoagulation at 4 days for your patients with GI bleeds

Use heparin bridging only in high risk patients and only at 48 hours post-op

Avoid dual antiplatelet therapy for stroke prophylaxis

Consider a shorter 5 day course of prednisone for AE-COPD


Summary

Know the precautions associated with quinolones including dysglycemia in diabetic patients and peripheral neuropathy

Consider monitoring for post-op cardiac ischemia in elderly hip fracture patients

Consider establishing objective criteria in your hospital for ICU admissions for cardiac and respiratory conditions, and for sepsis

Use Choosing Wisely for quality improvement projects in your hospital


Important recent practice guidelines 2012-13 Guyatt GH, Akl EA, Crowther M, Gutterman DD, Schuunemann

HJ;American College of Chest Physicians Antithrombotic Therapy and Preventionof Thrombosis Panel. Executive summary: Antithrombotic Therapy and Prevention of Thrombosis, 9th ed: American College of Chest Physicians Evidence-Based Clinical Practice Guidelines. Chest. 2012;141:7S-47S

Carson JL, Grossman BJ, Kleinman S, Tinmouth AT, Marques MB, Fung MK, et al; Clinical Transfusion Medicine Committee of the AABB. Red blood cell transfusion: a clinical practice guideline from the AABB. Ann Intern Med. 2012;157:49-58

Umpierrez GE, Hellman R, Korytkowski MT, Kosiborod M, Maynard GA, Montori VM, et al; Endocrine Society. Management of hyperglycemia in hospitalized patients in non-critical care setting: an endocrine society clinical practice guideline. J Clin Endocrinol Metab. 2012;97:16-38

Jneid H, Anderson JL, Wright RS, Adams CD, Bridges CR, Casey DE Jr, et al; 2012 Writing Committee Members. 2012 ACCF/AHA focused update of the guideline for the management of patients with unstable angina/non-St elevation myocardial infarction : a report of the American College of Cardiology Foundation/ American Heart Association Task Force on practice guidelines. Circulation. 2012;126:875-910

Dellinger, RP, et at. Surviving Sepsis Campaign Guidelines Committee including the Pediatric Subgroup. Surviving sepsis campaign: international guidelines for management of severe sepsis and septic shock: 2012. Crit Care Med. 2013 Feb;41(2):580-637 Update in Hospital Medicine 2013

Studies Sites

Villanueva C, Colomo A, Bosch A, Concepción M, Hernandez-Gea V, Aracil C, Graupera I, Poca M, Alvarez-Urturi C, Gordillo J, Guarner-Argente C, SantalóM, Muñiz E, Guarner C. Transfusion strategies for acute upper gastrointestinal bleeding. N Engl J Med. 2013 Jan;368(1):11-21.

Witt DM, Delate T, Garcia DA, et al. Risk of thromboembolism, recurrent hemorrhage, and death after warfarin therapy interruption for gastrointestinal tract bleeding. Arch Intern Med. 2012;172:1484-91

Tafur AJ, McBane R 2nd, Wysokinski WE, et al. Predictors of major bleeding in peri-procedural anticoagulation management. J Thromb Haemost. 2012;10:261-7.

Meng Lee, MD; Jeffrey L. Saver, MD; Keun-Sik Hong, MD, PhD; Neal M. Rao, MD; Yi-Ling Wu, MS; and Bruce Ovbiagele, MD, MS Risk–Benefit Profile of Long-Term Dual- Versus Single-Antiplatelet Therapy Among Patients With Ischemic Stroke A Systematic Review and Meta-analysis Ann Intern Med. 2013;159:463-470.

Chou HW, Wang JL, Chang CH, et al Risk of severe dysglycemia among diabetic patients receiving levofloxacin, ciprofloxacin, or moxifloxacin in Taiwan Clin Infect Dis. 2013 Published on line Aug 15, 2013


Studies Sites

US Food and Drug Administration. FDA Drug Safety Communication: FDA requires label changes to warn of risk for possibly permanent nerve damage from antibacterial fluoroquinolone drugs taken by mouth or by injection. http://www.fda.gov/downloads/Drugs/DrugSafety/UCM365078.pdf

Leuppi JF, Schuetz P, Bingisser R, et al. Short-term vs. conventional glucocorticoid therapy in acute exacerbations of chronic obstructive pulmonary disease: the REDUCE Randomized Clinical Trial. JAMA. 2013;390(21):2223-2231

Gupta BP, Huddleston JM, Kirkland LL, et al. Clinical presentation and outcome of perioperative myocardial infarction in the very elderly following hip fracture surgery. J Hosp Med. 2012;7:713-6.

Delgado MK, Liu V, Pines JM, et al. Risk factors for unplanned transfer to intensive care within 24 hours of admission from the emergency department in an integrated healthcare system. J Hosp Med. 2013;8:13-9

Choosing Wisely, Society of Hospital Medicine – Adult Hospital Medicine, Five Things Physicians and Patients Should Question http://www.choosingwisely.org/doctor-patient-lists/society-of-hospital-medicine-adult-hospital-medicine/


Disclosures and Conflicts of Interest

I WISH! None

QUESTIONS?


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