Thromboprophylaxis in ICU Thomas Li Consultant respiratory physician Union Hospital Thromboprophylaxis in ICU

Receive no sponsorship from any drug company or medical device company Declare no conflict of interest with any drug company or medical device company

Guidelines of VTE prophylaxis Development of local guideline Mechanical methods of VTE prophylaxis Other strategies for early detection of VTE Routine USG screening Low threshold CTPA Restriction of sedation Early rehabilitation

If you are preparing for an ICU exam

International guidelines American College of Chest Physicians Surviving Sepsis Campaign Institute of Healthcare Improvement National Institute of Health and Care Excellence

Who are at risk ? Medical patients Surgical patients Mobility significantly reduced ≥ 3 days Reduced mobility + any VTE risk Surgical patients Anaesthetic time > 90 minutes Anaesthetic time > 60 minutes + operation involves pelvis or lower limb Acute surgical admission with inflammatory or intra-abdominal Expected reduced mobility Any VTE risk factors NICE guideline

Increased risk of VTE Active cancer or cancer treatment Age > 60 years Intensive care admission Dehydration Known thrombophilia BMI > 30 1 or more significant medical comorbidity Personal or family history of VTE Use of HRT or contraceptive Varicose veins with phlebitis NICE guideline

Increased risk of bleeding Active bleeding Acquired bleeding disorders eg liver failure Concurrent use of anticoagulant LP, epidural or spinal anaesthesia in coming 12 hours LP, epidural or spinal anaesthesia within past 4 hours Acute stroke Platelet < 75 BP > 230/120 Untreated inherited bleeding disorders

Position statement on prevention of VTE in ICU in HK Local epidemiological studies without pharmacological prophylaxis Mixed ICU patients: 11% with femoral vein cannulation had iliofemoral DVT (Joynt et al. CHEST 2000) Medical ICU patients: 8% above knee DVT, 11% below knee (Joynt et al. HKMJ 2009)

Other Asian countries 10.5% (20/190) surgical ICU patients without thromboprophylaxis in Thailand had DVT 4.7% (9/190) were proximal DVT 3.7% (7/190) had PE confirmed by CT (Asian J Surg 2009;32:85) In a neurorehab ward in Singapore 98% not on heparin 77% Chinese, 14% Malay, 7% Indian Proximal DVT 2.6%(11/419), distal 2.4%(10/419) (Arch Phys Med Rehabil 2008)

Position statement on prevention of VTE in ICU in HK Graduated compression stockings (GCS) and intermittent pneumatic compression (IPC) devices are commonly used Most except a few ICUs use pharmacological DVT prophylaxis

Position statement on prevention of VTE in ICU in HK No RCT on prevention of VTE in Chinese critically ill patients could be identified 5 RCT on prevention of VTE in Chinese patients could be identified

Thromboembolic prophylaxis for TK arthroplasty in Asian patients DVT/ PE Control Number (%) GCS IPC Enoxaparin P-value Overall 24 (22) 14 (13) 9(8) 6 (6) 0.001 Proximal DVT 3 (3) 1 (1) 0 (0) 0.279 Distal DVT 21 (19) 13 (12) 9 (8) 5 (5) 0.003 Symptomatic PE 0.571 > 90% were ethnic Chinese Journal of Orthopaedic surgery 2009

Thromboembolic prophylaxis for TK arthroplasty in Asian patients Compare % of DVT P value Control vs GCS 22 vs 13 0.119 Control vs IPC 22 vs 8 0.032 Control vs enoxaparin 22 vs 6 0.001

Bleeding complications Control GCS IPC Enoxaparin Median transfusion Units/person 0.1 0.2 0.34 Bleeding complications Number of patients 3 4 9

Authors support use of IPC instead of LMWH

LMWH as DVT prophylaxis for Asian colorectal surgical patients Enoxaparin 20 mg Q12H preop Enoxaparin 40 mg daily for at least 4 days post-op 5/169 in control group had DVT, 3 out of the 5 DVTs also had acute pulmonary embolism 0/134 on enoxaparin had DVT/ PE (P=0.045) 3/169 in control had bleeding related complications 9/169 had bleeding complications (1 subdural haematoma and 2 intra-abdominal bleed exploration) (P=0.037) Authors supported use of LMWH Dis Colon Rectum 1999

DVT in HK Chinese with hip fractures: Incidence and effects of LMWH 37% (29/ 78) developed DVT No difference in incidence between 2 groups LMWH may reduce proximal DVT Arch Orthop Trauma Surg 1999

Position statement on prevention of VTE in ICU in HK Best available evidence do not address the benefits and risks of Chinese critically ill patient regarding pharmacological prophylaxis RCT in Chinese critically ill patients are needed

End of discussion ?

What else can we use to prevent/ manage DVT or VTE ? Mechanical devices Routine screening Low threshold for CT Early mobilization

How effective in mechanical devices ? Systemic review MEDLINE, EMBASE, Biosis, Derwent Mostly surgical patients Mechanical devices (GCS or IPC or foot pump) reduce risk of DVT by 2/3 as monotherapy reduce risk of DVT by ½ when combined with pharmacological prophylaxis reduce risk of proximal DVT by ½ Reduce risk of PE by 2/5 Health Technology Assessment 2005

ACCP 2008 guideline Appropriate size Proper fitting Compliance Storage Disinfection

Is graduated compression stocking (GCS) harmless ? CLOTS 1 study Multi-centre, international, UK, Australia and Italy 2518 patients admitted to hospital within 1 week of onset of acute stroke > 80% were ischaemic stroke Randomized thigh length GCS or control USG at day7-10 and day 28-30 CLOTS trial collaboration Lancet 2009

Is graduated compression stocking (GCS) harmless ? GCS Control Proximal DVT 10% 10.5% Skin ulcers Blisters 5% 1% Necrosis

CLOTS 2 trial: Thigh-length vs below knee stockings for DVT prophylaxis after stroke Multi-centre, international randomized 3114 patients hospitalized within 1 week of acute stroke (>80% were ischaemic) Thigh length DVT or below knee DVT Prematurely stopped enrollment because of results of CLOTS 1 trial Ann Intern Med 2010

Thigh length Below-knee CLOTS 2 trial: Thigh-length vs below knee stockings for DVT prophylaxis after stroke Thigh length Below-knee Proximal DVT 6.3% 8.8% P=0.008 Death 10.9% 10.3% Any skin Problem 9% 6.9% P=0.03 Skin Breakdown 3.9% 2.9%

Why ? Risk of DVT No stocking = Thigh length stocking < below knee stocking ? Increased risk of DVT with below knee DVT If we believe the results, avoid the use of GCS for DVT prevention in patients after stroke

Why screen for DVT ? It is present among our patients, but may be of lower prevalence than other ethnic groups Controversy in use of pharmacological prophylaxis Some patients have obvious contraindication to heparin or LMWH and may need IVC filter It is clinically silent

DVT is clinically silent in ICU 239 patients surgical-medical ICU patients Twice weekly USG Structural clinical examination DVT risk score calculated Journal of Critical Care 2005

DVT is clinically silent in ICU DVT risk scores used in symptomatic outpatients were not applicable in ICU Universal prophylaxis or routine screening

Potential risk factors in critically ill Chinese medical ICU patients Only 4/15 of Confirmed DVT had signs 11/15 had no signs Joynt et al HKMJ 2009

Routine USG screening for DVT Very few ICUs have access to portable ultrasound for diagnosis of DVT Impractical to transport critically ill patients to radiological department regularly & frequently for ultrasound examination Can intensivists do USG for diagnosis ?

A common scenario when I am on call in ICU One night at 2 am, an ICU nurse call you patients in bed 1, 4, 5 and 7 have “desaturations” What will be your reply ?

Your reply Ask the nurse to continue observation & sleep Examine each patients and reassure the nurse Examine each patients + ECG Examine each patients + ECG + portable CXR Examine each patients + ECG + portable CXR + wake up the on-call radiologist for urgent CT pulmonary angiogram

Diagnosis of acute pulmonary embolism in critically ill

Continuous SpO2 monitoring and static lung compliance Continuous SpO2 and diagnosis of pulmonary embolism in critically ill trauma patients Continuous SpO2 monitoring and static lung compliance >10% drop in SpO2 and no change in compliance 48 out of 972 critically ill trauma patients in 18 months 44% of these patients had PE demonstrated using pulmonary angiogram J Trauma 2001

Virchow’s triad Hypercoagulability Haemodynamic changes (Stasis or turbulence) Endothelial damages or dysfunction

Daily interruption of sedation Intervention N= 68 Control N= 60ntrol P-value Duration of mechanical ventilation 4.9 7.3 0.004 ICU stay 6.4 9.9 0.02 Hospital stay 13.3 16.9 0.19 Extubation rate 4% 7% 0.88 Kress et al. NEJM 2000

No sedation for critically ill on mechanical ventilation: RCT Sedation with daily interruption P-value Days without ventilation 13.8 9.6 0.019 ICU stay 13.1 22.8 0.032 Hospital stay 34 58 0.004 Agitation 20% 4.7% Lancet 2010

Early mobilization in ICU Daily interruption of sedation + early mobilization Daily interruption of sedation P-value Return to independent daily living at hospital discharge 59% 35% 0.02 Duration of delirium 2 days 4 days Ventilator-free days 23.5 21.1 0.05 Lancet 2009

Recommendations Multidisciplinary approach to prevent VTE Early mobilization and rehabilitation Reduction in use of sedatives and muscle relaxants Compression devices for patients with high bleeding risks Avoid femoral vein cannulation Frequent regular USG screening for DVT

Recommendations Remove central venous catheters as soon as possible Low threshold for CT pulmonary angiogram for unexplained hypoxaemia Consider pharmacological prophylaxis after balancing the risks and benefits

What the colleges and society can do ? Encourage collaboration between different ICU for multicenter studies on local Chinese patients Liaise with college of radiology to organize recognized training in ultrasound diagnosis of DVT for intensivists