1. Needlestick Injuries: Medical Evidence and Legal Issues Emergency Medicine Grand Rounds Nov 29 th, 2001 Ian Walker, CCFP(EM)

2. Objectives Review the literature regarding needlestick injuries Determine how one accurately assesses risk Review the evidence for and current recommendations regarding PEP Review some legal issues and current CRH policy re: source patient testing

3. Epidemiology Actual seroconversion uncommon 94 confirmed cases worldwide prior to 1997 Exposure very common Up to 52% of HCW report at least one prior needlestick, and 24% report one in the past year. Risk depends on prevalence of HIV Calgary wide ~ 0.5% Amongst needle users ~ 5%

4. Canadian Data Canadian Needlestick Surveillance Network – April 1 to Sept 30, 2000 599 exposures at 10 sites nationwide 209 at FMC Overall, 1.8 exposures per 100 FTE Nurses incurred ~56% of these

5. High Risk Groups

6. Location of Exposures

7. What is the Risk? Generally quoted as 0.3% for percutaneous exposures Based on meta-analyses of multiple small prospective series Aggregated data from 23 studies 6202 exposures, 20 seroconversions 0.32% conversion rate (CI 0.20%-0.50%) Wide range of types of exposure

8. Muco-cutaneous Exposure Skin and mucus membrane exposure risk poorly quantified Mucus membrane risk quoted as 0.09% Based on a single case out of 1107 documented exposures ICU nurse manipulating an arterial catheter in a hemophiliac patient – “hands, eyes, mouth splashed with very large amounts of blood”

9. Non-Intact Skin Cases of seroconversion have been reported following exposure to non-intact skin Exact risk not quantified due to infrequency of event Estimated by the CDC to be less than that for mucus membrane exposure Infection following exposure to intact skin has not been reported 2712 exposures with no seroconversion (95% CI 0 to 0.1%)

10. Risk Assessment Related to two variables 1. The amount of blood to which the patient is exposed 2. The amount of HIV in the exposed blood (i.e. the viral load of the source patient) Traditionally, “risk assessments” done for patients of unknown HIV status Increasingly unreliable In 1985, 94% of all AIDS patients had a major RF In 1996, 20% of all patients had been infected through heterosexual contact or had no known RF

11. One Case-control Study 33 cases (seroconverted), 665 controls Factors associated with increased risk of HIV seroconversion Deep injury (OR = 15) Visible blood on device (OR = 6.2) Procedure involving artery or vein (OR = 4.3) Terminal illness in source pt. (OR = 5.6) Cardo, et al. “A Case-control Study of HIV Seroconversion in Health Care Workers after Percutaneous Exposure” NEJM 337:21, pp. 1485-90. 1997

12. Non-Risks Some factors surprising not associated with increased risk. Large bore needles Use of gloves Hollow bore vs. suture needles

13. Clinical Condition of the Source In the NEJM study, advanced terminal disease in the source pt associated with increased risk. Another study looked at source pt’s disease Asymptomatic: 0 conversions out of 148 AIDS: 4 conversions out of 889 Reasonable to conclude that advanced disease in the source is a risk factor

14. Loose Needles What of cleaning staff who get a percutaneous exposure of unknown significance? No data available Risk assessment based on prevalence of HIV amongst possible source pts Risk generally regarded as very low

15. Post-Exposure Prophylaxis Does it work? Most data from animal studies Many use Simian Immunodeficiency Virus Inoculums generally large Delay to drug administration varies Indirect evidence from maternal – fetal studies

16. Human Studies Attempt to carry out an RCT unsuccessful Only 84 patients enrolled over >1 year New trial probably now unethical The NEJM case-control study Looked at AZT use Cases less likely to have used AZT (OR 0.19, p=0.003) Hence the quoted 80% reduction (CI 43%-94%) ARR = 0.24%, NNT = 417!!

17. Limitations of the Evidence Animal studies represent poor models for occupational human exposure Retrospective studies subject to many biases Perinatal exposure fundamentally different from occupational exposure AZT PEP has been documented ineffective in at least 21 cases worldwide. 6 Cases of ineffective combination therapy

18. The “2 Hour Window” Extrapolated from animal studies & our understanding of HIV pathogenesis Most studies done with primates, with PEP given within 24 hrs being effective. Efficacy decreases at 48hrs Efficacy also decreased when regimen shortened to 3 or 10 days Bottom line – the sooner the better

19. Who Should Get PEP? For needlesticks, can think in terms of source factors and exposure factors: Known HIV +’ve source Advanced disease in the source patient Visible blood on needle Needle from artery or vein Deep injury A matter of multiplying risks

20. What Do I Give? Studies all done with AZT alone for prophylaxis (either peri-natal or occupational) Addition of Lamivudine (3TC) generally recommended Concern re AZT resistance Demonstrated superiority of combination therapy in HIV +’ve patients Addition of protease inhibitor (PI), i.e. Indinavir or Nelfinavir in high risk cases Early enthusiasm for Nevirapine (an NNRTI) tempered by serious hepatic toxicity

21. Current CDC Guidelines Evaluation Test source patients for HBsAg, Anti-HCV, and HIV antibody Direct virus assays not recommended Consider rapid HIV test If source is negative, no further follow up recommended (OH&S?) Unknown or un-testable source Assess risk of bloodborn pathogen in general population or individual patient if known.

22. Current CDC Guidelines Treatment Recommended when source patient is HIV +’ve or deemed likely to be 2 Drug PEP Less severe exposures (see RF’s) to an asymptomatic HIV +’ve source Exposure to unknown source where HIV infection likely Exposure to source with unknown HIV status but with RF’s (IVDU, etc…)

23. Current CDC Guidelines Treatment, cont. 3 Drug PEP More severe exposure to asymptomatic or symptomatic HIV +’ve source Less severe exposure to a symptomatic HIV +’ve source (incl acute seroconversion) With mucous membrane exposures, same recommendations apply “Large volume” is considered a severe exposure “Small volume” (i.e.. a few drops) is less severe

24. When to Speak to ID Pregnant or breast feeding patients Source patient already on retrovirals Delayed exposure Significant renal or hepatic disease Unknown source

25. CHR OH&S Policy Patients referred to ED if source known positive or high risk Surveillance only if low or unknown risk Routine exposures treated with AZT/3TC More significant exposures get the addition of Nelfinavir (Viracept™)

26. Rapid POC Testing Rapid HIV testing now widely available, inexpensive and reliable Blinded study comparing to non-rapid assays and Western blot yielded a sensitivity of 100% and a specificity of 99.1% (7 false positives out of 837) One ED based study evaluated two rapid assays in 495 consecutive patients Correctly identified all 25 positives One false positive, No false negatives

27. Rapid Testing In Calgary CLS uses an assay which is equivalent to the “Determine” Assay by Abbott Sensitivity and Specificity both 99.9% Done in the on-site rapid response labs Current turn around time 1 hr 24 min Confirmed by Western Blot at Prov Lab Reagent costs ~$7 per test Majority of costs due to “STAT” processing Can be done as an “add-on” to serum sample

28. Compliance Issues Two or three drug regimens generally well tolerated More side effects attributable to PI than to AZT / 3TC Serious adverse events few Given high NNT, concerns raised over NNH 2 Cases of fulminant hepatic failure with Nevirapine

29. The HIV PEP Registry Conducted 1996-1999 by the CDC Voluntarily enrolled 492 potential HIV exposed HCW’s who received PEP Followed to 6 weeks Monitored for regimen, compliance, common and serious adverse events Not a controlled study

30. PEP Regimes 17 different regimes used Most commonly AZT & 3TC (36%) AZT, 3TC & Indinavir (45%) AZT, 3TC & Saquinovir (5%) AZT, 3TC & Nelfinavir (3%)

31. Compliance 449 patients with FU data 47% completed PEP 9% discontinued one drug 44% discontinued all drugs 50% due to symptoms 48% source pt tested negative

32. Adverse Events - Common Most common: nausea (57%) Vomiting & Diarrhea (14% & 16%) Headache (18%) Fatigue or Malaise (38%) Mean time to onset of symptoms 3 or 4 days for all of the above Not able to determine what proportion attributable to PI’s as opposed to others

33. Adverse Events - Serious Defined as life threatening, permanent or requiring hospitalization 6 cases 1 case of fever and rash on 5 drug regime 2 cases of renal colic on AZT/3TC/IDV 1 on day 3, 1 on day 23 2 cases of severe N&V on AZT/3TC/SQV Occurred on days 3&4 1 case of bizarre episodic eye movements and blurred vision which occurred on day 2

34. Legal Issues A large part of making an appropriate assessment is determining the HIV status of the source patient. What if the patient won’t, or can’t consent? Issue of testing unconscious, incompetent or dead patients becoming increasingly prominent.

35. Current Alberta Legal Status Issue governed by common law States that any medical intervention must be consented to (otherwise it is assault) In emergency situations, can assume consent for procedures that are therapeutic. Surrogate consent has no legal standing Other provinces (i.e. Ontario) have legislation which legitimizes surrogate consent for non- therapeutic procedures.

36. The Arguments Patient’s right to privacy Positive test has implications for work, housing, mental health, interpersonal relationships, insurance, etc… Patient may not want to know If tested, then we have an obligation to inform patient of a positive result.

37. The Counter Arguments Information has implications for the health care worker Anxiety Potentially unnecessary exposure to toxic drugs Risk of exposure can be minimized, but not avoided In event of seroconversion, still have obligation to inform source patient, so needlestick recipient becomes a “surrogate test”

38. Current MAB Policy Newly approved blanket consent form for new admissions Authorizes testing in the case of exposure Does not cover patients admitted emergently through ER, trauma pts, etc… Legally uncertain but deemed “defensible” Still no recognition of surrogate consent MAB limited by lack of legal standing

39. What Can You Do? Hon David Hancock Attorney General of Alberta #208, 10800 - 97 Avenue Edmonton, AB T5K 2B6 Phone: (780) 427-2339 Fax: (780) 422-6621 Hon Gary Mar Minister of Health & Wellness #323, 10800 - 97 Avenue Edmonton, AB T5K 2B6 Phone: (780) 427-3665 Fax: (780) 415-0961

40. Take Home Message PEP likely effective in decreasing rate of seroconversion after significant HIV exposures Risk assessment includes Status or degree of risk of source Depth of injury Presence of visible blood Procedure involving artery or vein

41. Take Home Message Rapid HIV testing helpful and reliable One or two doses of PEP usually well tolerated Average risk patients – Combivir High risk patients – Combivir & Nelfinavir Involve OH&S Write to your MLA if concerned about the legality of testing source patients