1. Sitting here in bed, can’t use my spirometer. Brewing DVT’s. Not to worry though ventilator air is clean and humidified. My stomach is sore I’ll ask the nurse for some more of those PPIs BM would be nice, I haven’t had one in days, PEG is best Hospital-Based Prophylaxis

2. Prophylaxis Pro·phy·lax·is, prōfəˈlaksəs, noun – Pro, Latin for ‘before’ – Phulaxis, Greek for ‘act of guarding’ – Action taken to prevent disease, especially by specified means or against a specified disease. 2014

3. “Preventative” Healthcare Primary: – Methods to avoid occurrence of disease. Most population-based health promotion efforts are type. Secondary: – Methods to diagnose and treat existent disease in early stages before it causes significant morbidity. Tertiary: – Methods to reduce negative impact of existent disease by restoring function and reducing disease- related complications.

4. Tiered Prevention Universal: – Involves the whole population and aims to prevent or delay the abuse of alcohol, tobacco, and other drugs. All individuals, without screening, are provided with information and skills needed to prevent the problem. Selective: – Groups at above average risk. May be distinguished by traits such as age, gender, family history, or economic status. Indicated: – Involves a screening process, and aims to identify individuals who exhibit early signs or risks.

5. Types & Examples Preventative – Hand washing– Breastfeeding – Immunizations– Nutrition – Exercise– Sexual education – Fluoride– Potassium iodide – Zinc– Vitamin A – Water sanitation– Antimalarial tx

6. Breastfeeding Jones, Lancet 2003; 362 (9524):1747-57.

7. Hospital-Based Prophylaxis Gastrointestinal prophylaxis Ventilator associated pneumonia Bowel regimens Deep vein thrombosis Anticoagulation therapy Antiplatelet therapy Antimicrobial prophylaxis in surgical pts Line care Foley catheters Fall prevention Insulin control

8. Hospital-Based Prophylaxis Gastrointestinal prophylaxis Ventilator associated pneumonia Bowel regimens Deep vein thrombosis Anticoagulation therapy Antiplatelet therapy Antimicrobial prophylaxis in surgical pts Line care Foley catheters Fall prevention Insulin control

9. Deep Vein Thrombosis Concern is VTE (venous thromboembolism), PE Prevention/prophylaxis – Ambulation – Calf exercises – Anticoagulation – Antiplatelet – Compression stalkings – SCD (sequential compression device) – Electrical stimulation of leg muscles

10. Pathophysiology Virchow Triad: – Venous stasis – Endothelial or vascular injury/insult – Hypercoagulability Typically begins inside the valves of the calf veins, with slightly decreased PaO2, thus activating biochemical pathways leading to coagulation

11. Risk Factors are Additive

12. The Guidelines Evidence-based guidelines from the American College of Chest Physicians (ACCP) – Specifically, 9 th edition guidelines from the Antithrombotic Therapy and Prevention of Thrombosis committee Acknowledgment of the “significant push in HC to administer DVT prevention for every patient, regardless of risk. As a result, many patients are receiving unnecessary therapies that provide little benefit and could have adverse effects.”

13. The Guidelines

14. DVT Clinical Problem 25+% of all cases of DVT/VTE are associated with hospitalization – 50-75% of cases of VTE occur in patients on the medicine service Prospective studies of high risk patients not on prophylaxis found 10.5-14.9% with DVTs by venography and 5% by US Antiplatelet Trialists’ Collaboration, BMJ 1994; 308: 235-46. Heit, Arch Intern Med 2000; 160: 809-15. Cohen, BMJ 2006; 332: 325-9. Samama, NEJM 1999; 341: 793-800. Leizorovicz, Circulation 2004; 110: 874-9.

15. DVT Clinical Problem Of the 10.5-14.9% w/ DVTs, 0.3-1.5% had VTE – Event rate = 0.02-0.14% NNT? – Assume VTE rate is 1.5% and prophylaxis eliminated ALL of this » NNT = 1/ARR = 1/0.015 = 67 patients – Assume VTE rate is 0.3% and prophylaxis eliminated ALL of this » NNT = 1/0.003 = 333 patients – Asymptomatic in > 70% of cases 67  20 333  33 – …So the symptomatic, potentially life-threatened 30% of patients we help with mechanical or chemical therapy, right?...

16. Bloody Problem with DVT/VTE Prophylaxis Prophylaxis is routine (F.A.S.T.H.U.G.) but benefits and risks are NEBULOUS Analyses of 10 trials comparing heparin prophylaxis to no VTE prophylaxis in 20k+ patients w/o stroke showed a reduction in PE (RR 0.69, CI 0.52-0.90) and no decrease in either the incidence of DVT OR MORTALITY! – Significant increase in bleeding in the heparin- treated patients (RR 1.34, CI 1.08-1.66)

17. Bloody Problem with DVT/VTE Prophylaxis In 8 trials of 15k+ patients w/ acute stroke, meta-analysis showed heparin prophylaxis resulted in NO STATISTICALLY SIGNIFICANT reduction in PE, DVT OR MORTALITY! – Statistically significant increase in MAJOR bleeding (RR 1.66, CI 1.20-2.28)

18. LMWH vs UFH In 9 trials of 11k+ patients there was no difference in mortality, PE, or major bleeding In 2,785 acute stroke patients in 5 trials – LMWH was equivalent to UFH NO DIFFERENCE in mortality, PE, symptomatic DVT or major bleeding

19. Continued LMWH Therapy In 6,085 IMMOBILE, hospitalized medical patients LMWH prophylaxis given for 10 days and patients randomized to stop or continue for an additional 28 days – Continued LMWH had a significant reduction in symptomatic VTE and a significant increase in major bleeding – NO DIFFERENCE in mortality, as compared with those randomized to no additional heparin prophylaxis – with NO INCREASED RISK!

20. LMWH in Acutely Ill Medical Patients NEJM 2011; 365: 2463-72 Double-blind, placebo-controlled, randomized trial Enoxaparin w/ elastic graduated compression vs. placebo w/ elastic graduated compression for 10 + 4 days Primary efficacy endpoint was RATE of death from ANY cause at 30days. Primary saftey endpoint was RATE of major bleeding DURING and < 48 hours after treatment (T 1/2 = 4.5 hours)

21. LMWH in Acutely Ill Medical Patients 8307 patients randomized Rate of death 4.9% in the enoxaparin group as compared with 4.8% in the placebo group (risk ratio, 1.0; 95% confidence interval [CI], 0.8 to 1.2; P = 0.83). – NNT = 1000 Rate of major bleeding was 0.4% in the enoxaparin group and 0.3% in the placebo group (risk ratio, 1.4; 95% CI, 0.7 to 3.1; P = 0.35). – NNH = 1000 Enoxaparin + stockings vs. placebo + stockings was NOT ASSOCIATED WITH A REDUCTION IN THE RATE OF DEATH (primary endpoint).

22. Mechanical devices - Stockings In 2,518 patients in one clinical trial and evidence from 3 reviews there is NO STATISTICALLY SIGNIFICANT DIFFREENCE in MORTALITY, PE, SYMPTOMATIC DVT as compared with NO STOCKINGS! (RR 4.02, CI 2.34-6.91) 2 RCTs compared LMWH to mechanical DVTP – Incidence of DVT in the mechanical group was higher, with no SS reduction in DVTs in mechanical group – Conclusion: Use a device that doesn’t work when you can’t anticoagulate!

23. Mechanical Devices - SCDs NO MECHANICAL DEVICE has been shown to reduce VTE rates or mortality – ACCP guidelines recommend against mechanical DVT prophylaxis in trauma patients (? trauma) Local tissue hypoperfusion can cause peripheral vascular compromise! – If incorrectly sized can cause tissue necrosis and ulceration ? Utility in diabetics and elderly – …Which accounts for what % of hospitalized patients?

24. Mechanical Devices - SCDs Non-compliance! – Prospective ICU study 78% compliance in the ICU – These patients can’t even move! 48% compliance once transferred to the floor! Observational study in high-risk trauma patients over 24 hour period: – 19% fully compliant – 53% devices functioning correctly – 61% of patients awake during non-compliant episodes

25. Hospital-Based Prophylaxis Gastrointestinal prophylaxis Ventilator associated pneumonia Bowel regimens Deep vein thrombosis Anticoagulation therapy Antiplatelet therapy Antimicrobial prophylaxis in surgical pts Line care Foley catheters Fall prevention Insulin control

26. Gastric Prophylaxis Physiology Rationale for stress ulcer prophylaxis – ICU – Wards Considerations Recommendations

27. Gastroprotection Gastric acidity Mucosal layer Tight intracellular junctions Peristalsis Innate and adaptive immunity

28. Gastric Mucosal Damage “Noxious” factors overwhelm innate defenses – Bacteria – Toxins (drugs, cytokines, etc.) – Acid Defense mechanisms are impaired – Hypoperfusion – Loss of barrier function

29. Stress-Related Mucosal Damage Numerous, small gastric erosions Worsened by gastric acid Primarily due to insufficient blood flow Primarily in fundus and corpus

30. Neurohormonal Regulation

31. In the ICU… Mechanical Ventilation ↑ Catecholamines ↑ Inflammatory Cytokines High PEEP ↓ Cardiac Output Splanchnic Hypoperfusion Altered Motility Loss of Barrier Function Bacterial OvergrowthMucosal InjuryErosionUlcerationSIRS/MODS

32. Who is at Risk? Ali, Gastroenterol Clin N Am 2009; 38: 245-65

33. Conventional Wisdom Sepsis/hypotension Prolonged ICU stay ( > 7 Days) Hepatic or renal fialure H/o PUD High-dose steroid use (250mg/day hydrocortisone or equivalent) > 35% BSA burn Post-organ transplant Head trauma w/ GCS < 10 Multiple traumas Ellison, Crit Care Med 1996; 26: 1974-81

34. Incidence in the ICU 75-100% w/ gastric lesions 15-50% w/ occult bleeding 5-25% overt bleeding 50% MOTRALITY in those with clinically significant bleeding! C AVEAT : Includes all comers – If you remove highest risk (ventilated > 48 hours, coagulopathy) NNT = 900!!! Chuong, Curr Mol Med 2008; 8: 253-7. Cash, Crit Care Med 2002; 30 (Suppl 6):S373-8.

35. Is a PPI Superior to H2RA? Meta analysis of 7 trials – 936 patients – Risk difference: 0.04 (CI ‐0.09 to 0.01) Outlier removed – Risk difference: ‐0.02 (CI ‐0.05 to 0.01) CONCLUSION: – No mortality difference Lim, Crit Care Med 2010; Feb 18 epub.

36. Non-ICU Patients? NO EBM GUIDELINES RECOMMEND PROPHYLAXIS! One large US study – 17,707 patients, IM wards over 4 years 73 nosocomial GIB (0.41%) – Only risk factor was full dose anticoagulation – No ∆ with ASA, NSAID or steroids – Acid suppression was NOT protective Grube, Am J Health-Syst Pharm 2007; 64: 1396-1400. Qadeer, J Hosp Med 2006; 1 (1): 13-20.

37. SUP in Non-ICU Patients 22-71% prescribed inappropriately No Difference b/w community and academic practices PPIs most often prescribed ~50% given inappropriate SUP are discharged on acid suppression as well

38. SUP Risks? Clostridium difficile (PPI; OR = 2, CI 1.28-3) CAP, HCAP Hip fracture Medication interaction (Clopidogrel) Leonard, Am J Gastroenterol 2007; 102: 2047-2056.

39. PPI-AP Compromise of stomach acidity (acid mantle) against colonization of acid-labile pathogenic bacteria which may then be aspirated – Drug-immune system interaction W/o omeprazole exposure, NK cells lysed 48.7% of target cells After exposure to physiologic doses of omeprazole, only 4.2% of cells were lysed – After rinsing the cells and removing omeprazole from the media, cells recovered 75% of their previous cytotoxicity

40. PPI-AP in the Community Nested case-control study (OR) 5551 cases of pneumonia from 364,683 individuals in the Netherlands documented by both chest radiograph and microbiological culture Patients using PPI were 4 times more likely to acquire PNA – regardless of appropriateness of therapy – It was also dose dependent – AND inversely related to duration to treatment!

41. Hospital-Based Prophylaxis Gastrointestinal prophylaxis Ventilator associated pneumonia Bowel regimens Deep vein thrombosis Anticoagulation therapy Antiplatelet therapy Antimicrobial prophylaxis in surgical pts Line care Foley catheters Fall prevention Insulin control

42. Bowel Regimen Osmotics Bulking agents Stool softeners (surfactants) Lubricants, emollients Stimulant = irritant Chloride channel activators Serotonin agonist

43. (Hyper)Osmotics Works in the colon Onset in 30 minutes to 3 days Glycerine suppositories, sorbitol, lactulose, PEG Risk of dehydration

44. Bulking agents Works in large and small intestine Onset in 12-72 hours Adds bulk and water to allow stools to pass more easily  improved peristaltic action Bran, fiber, psyllium husk, methylcellulose, etc Risk of obstruction, dehydration

45. Stool softeners (surfactants) Works in large and small intestine Onset in 12-72 hours Acts as surfactant, enabling water and fat to be incorporated into the stool Docusate (Colace) Risk of malnutrition, hypovitaminosis, dehydration, loss of mucosal protection

46. Lubricants, emollients Works in colon Onset in 6-8 hours Lubricates stool to allow easier passage and retards colonic absorption of water Mineral oil Decreased absorption of fat-soluble vitamins, hypovitaminosis, dehydration

47. Stimulant = irritant Variable action in colon small intestine and rectum Onset in 15 minuted to 12 hours Stimulate intestinal mucosa and nerve plexus, altering water and electrolyte secretion. Stimulate peristaltic action. The most powerful laxative. Bisacodyl, castor oil, phenolphthalein, senna, cascara

48. Chloride channel activators Uncommonly used Increases intestinal osmotic gradient and stool hydration, motility Lubiprostone Management of chronic idiopathic constipation, IBS

49. Serotonin agonist Tegaserod, cisapride, prucalopride NEVER, EVER USE, EVER! Activation of 5-HT4R in enteric NS Cardiovascular side-effects

50. Hospital-Based Prophylaxis Gastrointestinal prophylaxis Ventilator associated pneumonia Bowel regimens Deep vein thrombosis Anticoagulation therapy Antiplatelet therapy Antimicrobial prophylaxis in surgical pts Line care Foley catheters Fall prevention Insulin control