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DA’s Despicable DVT / PE Prophylaxis. November 4, 2009 Surgery Rotation Sandra Katalinic Pharmacy Resident. Outline. Objectives Patient Profile Presentation Medications Review of Systems Lab Values Disease States Signs and Symptoms Risk Factors Pathophysiology - PowerPoint PPT Presentation
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DA’s Despicable DVT / PE Prophylaxis
November 4, 2009
Surgery Rotation
Sandra Katalinic
Pharmacy Resident
Outline
• Objectives• Patient Profile
– Presentation – Medications – Review of Systems – Lab Values
• Disease States– Signs and Symptoms– Risk Factors– Pathophysiology– Treatment Options
Outline
• Pharmacy Assessment– Drug Related Problems – Goals of Therapy – Clinical Question
• Literature Review– Chest Guidelines – 1˚ article– Therapeutic Options
• Outcome– Monitoring
Objectives
• Explain the procedure of a hemicolectomy with re-anastomosis
• List the risk factors for VTE• List the symptoms of DVT/PE and diagnostic
options• State the Chest Guideline’s DVT / PE
prophylaxis recommendation for cancer patients undergoing surgery for their cancer
Our Patient
• DA 57 y/o man• Admitted for right hemicolectomy w/ re-
anastomosis• The story:
– Originally scheduled for knee replacement– Found to be anemic– Colonoscopy revealed GI bleed tumor on
splenic flexure– Surgery = tumor on hepatic flexure– Extended right hemicolectomy w/ lymph nodes
Our Patient
• Allergy NKA
• PMHHypertension, anemia, hypokalemia
• FH Father = HTN
• SH Non-smoker, well balanced diet, non-coffee drinker,
rarely drinks ETOH
Home Meds
• Ramipril 10mg PO daily• Atenolol 50mg PO daily• HCTZ 12.5mg PO daily• KCl 600mg PO daily• ASA 81mg PO daily• B12 injection once monthly
Hospital Meds
• Cefazolin 1g IV on call to OR• Metronidazole 500mg IV on call to OR• Heparin 5000 units SC BID• APAP 1000mg PO q6h (ATC)• Ibuprofen 60mg PO q6h (ATC)• Morphine PCA 2mg/ml • Morphine 20 mg PO QID (Post PCA)• Morphine 5-10mg SQ q4h prn• Morphine 1-5mg IV q4h prn• Dimenhydrinate IV/IM/PO 25-50mg q4h prn• Ondansetron 4mg IV q8h prn• Naloxone 0.1mg IV prn• Diphenhydramine 25-50mg IV/IM/PO q4h prn• D5 ½ NS + 20mEq K+/L @ 125cc/hr• Zopiclone 3.75-7.5mg PO qhs• + Home meds (ramipril, atenolol, HCTZ, ASA)
Review of Systems
CNS Ø dizziness, lightheadedness, nausea
HEENT, RESP Ø SOB, cough; HEENT = unremarkable, no complaints
CVS Hx of HTN + anemia, Ø other known CV disease / chest pain
GI/GU Colon cancer, diet = full fluids, Ø vomiting or BM’s, small flatus
Liver, Kidney, Endocrine Ø history of diabetes, hyper/hypothyroid or other endocrine disorders, Foley catheter draining clear urine
Musc/extr/skin/fluids tenderness to surgical site, Ø sign of infection, Ø extremity swelling
Vitals
Oct 14 Oct 15 Oct 16
BP (mmHg)
125/75 135/75 120/65
HR (bpm)
87 105 107
RR (rpm)
18 18 18
O2Sat (%)
93 94 93
Temp (˚C)
37 39 37.5
Labs
Parameter Oct 14, 2009 Oct 15, 2009 Oct 16, 2009
WBC (x109/L) 10.8 13.5 6.7
Hgb (g/L) 99 105 97
MCV (fL) 74.0 75.0 73.9
Platelet (106/L)
403 382 334
Na (mmol/L) 133 133 135
K (mmol/L) 3.4 4.0 3.5
Cl (mmol/L) 98 96 95
CrCl (ml/min) 111.5 99.6 105.2
The Surgery
Risk Factors
• Increased age• Previous VTE• Major illness (CHF)• Major surgery (general anesthesia >30min)• Paralysis• Obesity• Trauma• Orthopedic surgery• Indwelling venous catheter• Genetic hypercoagulabilities• Estrogen replacement• SERMs• HIT
Venous Thromboembolism
• A blood clot which typically forms in lower extremities– Stays there = DVT– Dislodges to lungs = PE
• Can occur anywhere, typically presents in the lungs or lower extremities
• Presentation differs depending on where the clot is
Deep Vein Thrombosis
• Occurs in the deep veins of the legs• Symptoms occur below the clot typically
occur in the calf• Symptoms: calf pain, swelling, redness, heat• 10-20% of general surgery patients get DVT• Diagnosis: ultrasound, D-dimer, venography
Pulmonary Embolism
• Clot in the pulmonary artery of the lungs or one of its branches
• Symptoms: dyspnea, tachypnea, and tachycardia, chest pain, cough
• Hemoptysis < 1/3 of patients• Cardiovascular collapse (cyanosis, shock,
and oliguria)
Complications
• The post-thrombotic syndrome: a long-term complication of DVT from damage to the venous valves
• Symptoms are similar to an acute thrombotic event: chronic lower-extremity swelling, pain, tenderness, skin discoloration, ulceration.
Cancer patients
• Cancer surgery seems to have at least 2x the risk of postoperative DVT and >3x the risk of fatal PE than similar procedures in non-cancer patients
• Tumor cells secrete pro-coagulants activate coagulation cascade and suppress levels of protein C, S and antithrombin
Prevention
• Post operatively:– Low molecular weight heparin– Unfractionated heparin– Fondaparinux
• All considered equally efficacious by the Chest Guidelines
DRP’s
Problem Meds DRP
DVT/PE prophylaxis
Heparin 5000 units SC BID
Not receiving enough drug, at risk of DVT/PE
Pain APAP 1000mg q6hIbuprofen 60mg q6hMorphine PCA 2mg/ml Morphine 20 mg PO QID (Post PCA)Morphine 5-10mg SQ q4h prnMorphine 1-5mg IV q4h prn
Risk of sedation, inadequate pain control,
Nausea Dimenhydrinate 25-50mg Ondansetron 4mg IV q8h prn
Risk of sedation, inadequate nausea control
DRP’s
Problem Meds DRP
Pruritus Diphenhydramine 25-50mg IV/IM/PO q4h prn
Risk of sedation, inadequate control of pruritus
Respiratory depression
Naloxone 0.1mg IV prn
At risk of pain (too much drug)
Sleep Zopiclone 3.75-7.5mg PO qhs
At risk of inadequately controlled insomnia,
morning grogginess
DRP’s
Problem Meds DRP
Hypokalemia D5 ½ NS + 20mEq K+/L @ 125cc/hr
At risk of hyper / hypokalemia (cramps, arrhythmia)
Hypertension Ramipril 10mg PO daily
Atenolol 50mg PO daily
HCTZ 12.5mg PO daily
At risk of hyper / hypotension (dizziness, lightheadedness)
Anemia No drugs ordered Indication but no drug ordered (fatigue, malaise, SOB)
Goals of Therapy
• Prevent development of PE / DVT– SOB, chest pain, cough, calf pain, swelling, fever
• Prevent long term complications – Recurrent VTE, post-thrombotic disorder
• Maintain mobility (as before surgery)• Minimize / prevent side effects
– Bleeding, bruising, HIT
PICO questions
• P = 57 year old male with newly discovered colon cancer who has undergone a right hemicolectomy for cancer treatment
• I = unfractionated heparin (UFH) regimen • C = Low molecular weight heparin (LMWH) regimen• O = post-operative DVT/PE prophylaxis?
• In a 57 y/o male with newly discovered colon cancer who has undergone a right hemicolectomy for cancer treatment, what is the recommended regimen for DVT/PE prophylaxis with either LMWH or UFH?
2008 Chest Guidelines
• 2.1.3. For higher-risk general surgery patients who are undergoing a major procedure for cancer, we recommend thromboprophylaxis with LMWH, LDUH three times daily, or fondaparinux (each Grade 1A)
• What is the evidence behind this?
Study #1
Low molecular weight heparin for the prevention of venous thromboembolism after abdominal
surgery.
Bergqvist D. British Journal of Surgery 2004; 91: 965–974.
Study #1
• 16 comparative studies published between 1980-2003
• Search: “heparin”, “surgery”, “abdominal or rectal or colorectal or rectum or colon”, “clinical trials”
• Evaluated general abdominal surgery, surgery in patients with abdominal surgery, colorectal surgery
Study #1
• Surgery in patients with abdominal cancer:• Multiple studies demonstrating therapeutic
equivalence of UFH and LMWH• TID dosing of UFH = LMWH daily or BID
– enoxaparin & nadroparin studied
• Higher dose LMWH is >effective than low dose (5000 units vs. 2500 units dalteparin) w/ no increased bleeding complications– Hypercoagulable state in cancer?
Study #1
• Additionally, this study claims– Colorectal surgeries carry ++ VTE risk (30%) and
4x risk for PE (compared to?)
A Randomized Study Comparing the Efficacy and Safety of Nadroparin 2850 IU (0.3 mL)
vs. Enoxaparin 4000 IU (40 mg) in the Prevention of Venous Thromboembolism
after Colorectal Surgery for Cancer
Simonneau G. et al. Journal of Thrombosis and Haemostasis. 2006; Vol 4: p. 1693–1700.
Study #2
Study #2
• 950 patients randomized to receive – Nadroparin 2850 units SC once daily + enoxaparin
placebo– Enoxaparin 4000 units SC once daily + nadroparin
placebo
• Results– Non-inferiority was not established (power?)– Nadroparin asymptomatic distal DVT
symptomatic DVT or PE, anemia, profuse peri-operative bleed, post-operative transfusions, total transfusions
• Study concluded: nadroparin = attractive option for colorectal cancer surgery
Therapeutic Options
• Unfractionated heparin– Equally as efficacious as LMWH– Cheaper than other alternatives– Currently in hospital = can be monitored as
required
• Low molecular weight heparin
• Fondaparinux
Risk Vs. Benefit
• Clotting Risk– Cancer– Colorectal surgery / surgery in general– Immobility post-op– Advanced age (>40)
• Bleed risk– Cancer surgery– Ibuprofen + ASA (no hx of ulcer / GI bleed)
Monitoring
• Low molecular weight heparin– Sx of DVT – leg pain, swelling, redness– Sx of PE – chest pain, SOB, cough, fever– Bleeding / bruising– Hemoglobin, platelets– HIT (drop in platelets >50% or count <100)
Outcome
• Recommended heparin 5000 units SC TID– Suggest consider d/c ibuprofen if concerned about
bleed risk
• Resident took my recommendation• Patient completed hospital stay (10 days)
without symptoms of DVT/PE or bleed• DVT/PE usually occur in first 2 weeks post-op
risk continues up to 3 months
Duration of therapy
• For selected high-risk general surgery patients, including some of those who have undergone major cancer surgery or have previously had VTE, we suggest that continuing thromboprophylaxis after hospital discharge with LMWH for up to 28 days be considered (Grade 2A).
References
• First Consult - http://www.mdconsult.com/das/pdxmd/lookup/168950262-2?type=med
• DiPiro JT. Et al. Pharmacotherapy: A Pathophysiologic Approach 7th Ed. McGraw Hill. New York. 2008; p. 331.370
• Chest Guidelines The Perioperative Management of Antithrombotic Therapy. Chest. 2008; 133: p.299S-339S.
• Bergqvist D. Low molecular weight heparin for the prevention of venous thromboembolism after abdominal surgery. British Journal of Surgery 2004; 91: 965–974.
• A Randomized Study Comparing the Efficacy and Safety of Nadroparin 2850 IU (0.3 mL) vs. Enoxaparin 4000 IU (40 mg) in the Prevention of Venous Thromboembolism after Colorectal Surgery for Cancer. Simonneau G. et al. Journal of Thrombosis and Haemostasis. 2006; Vol 4: p. 1693–1700.
• Comparison of a Low Molecular Weight Heparin and Unfractionated Heparin for the Prevention of Deep Vein Thrombosis in Patients Undergoing Abdominal Surgery. The European Fraxiparin Study (EFS) Group. British Journal of Surgery. 1988; Vol 75(11): 1058-1063.