Michael C. Klein Centre Community Child Health Research

1. Israeli Family Physicians: what to know?Throwing the Mother Out with the Bathwater—Misuse of randomized controlled trials Michael C. Klein Centre Community Child Health Research BC Research Institute for Children’s and Women’s Health Emeritus Professor of Family Practice and Pediatrics University of British Columbia

2. Variation surfaces—BC Women’s Hospital 1993----- 25 docs 75% or more

3. Family Physicians Nullip SVD Episiotomy RatesApr 95-Mar 96: mean rate=19.2Apr 96-Mar 97: mean rate=14.9April 98-Mar 99 2 remaining

4. Variation surfaces Vancouver CQI 1993

5. Does Epidural Analgesia Increase the Likelihood of Cesarean Section? • How many think it does? • How many think it does not?

6. Epidural Cxion

7. A natural experiment at nearby community hospital • In early 1990s Community Hospital had Cxion rate of about 8%, while Women’s about 20% • We Created matched cohort of healthy women • Odds of having a Cxion at the tertiary care centre vs community 3.4 (CI 2.1—5.4) • Why? • More advanced cervical dilation on arrival (opportunity for doulas) • Use of epidural analgesia—largest effect: Epidural rate of 15.4% community, 67.2% tertiary Janssen P, Klein MC. Differences in Institutional Cesarean Delivery Rates: The role of pain management. J Fam Pract 2001; 50(3):217-223

8. A natural experiment at nearby community hospital • Differences between the hospitals: • Increased ambulation at the community (12% vs 5%) • Fewer numbers of caregivers for each woman at community • More oxytocin augmentation at community (32.3 vs 24.9%) • Less offering of epidural at community (qualitative) 16.7% vs 42.3% • Strong Head of OB at community who worked collaboratively with strong nursing and FP leadership, and together developed a coherent philosophy of care

9. A natural experiment at nearby community hospital • But when controlled for epidural, the Cxion rate at the two hospital was the same, about 12% • In other words, women with an epidural in each facility had a similarly high Cxion rate and women not receiving an epidural had a similarly low Cxion rate • Only real difference was: community hospital used epidural less often, and in so doing had a low Cxion rate • When Head of OB retired and nursing leadership also changed, the epidural and Cxion rate at the community hospital rapidly reached usual levels for BC Janssen P, Klein MC. Differences in Institutional Cesarean Delivery Rates: The role of pain management. J Fam Pract 2001; 50(3):217-223

10. Meanwhile Departmental CQI evolved into research • We studied natural variation in relation to physician epidural rates • Maternal outcomes • Newborn outcomes • The physician rather than the woman as the unit of analysis

11. Nulliparous Maternal Outcomes by Epidural Cohorts

12. Nulliparous Malposition (OP-OT) Rates by Epidural by Race

13. Nulliparous Oxytocin Augmentation Rate by Epidural Cohorts by Race

14. Nulliparous Cesarean Rate by Epidural Cohorts by Race

15. Epidural study

16. Nulliparous NCN/SCN Admission Rates by Epidural by Race

17. Were the physicians who were in each epidural cohort practicing differently? • Not only did they use epidurals less often, but • Used epidurals later • Spent more time with their patients in hospital--even though their patients spent less time in hospital • Indeed they practiced differently—more intimacy and engagement

18. Conclusion: • Physicians who employ epidural analgesia often (and early) in labor expose them to higher intervention rates and more adverse maternal and newborn outcomes than those who on average employ epidural analgesia less often and later in labor.

19. But not the fault of the anesthesia establishment at BC Women’s or likely elsewhere. Anesthesia provides an excellent service. They help us resolve many problems It is we who ask for help!!!!!!!!! At least at BC Women’s, there is no evidence that anesthetists are scavenging for business There is evidence from rural family practice (Stuart Iglesias) that epidurals can be introduced and associated with lowering of Cxion rate But that study requires contextual or environmental analysis

20. The Tyranny of Meta-analysis And the misuse of Randomized Controlled Trials

21. Collateral damage or Blowby—think Iraq • Or throwing the mother (and at times the baby) out with the bathwater. • Or consequences of left-sided thinking—what about the right side (think right brain)

22. David Sackett: understanding clinical trials. BMJ 309: 1994 • Information from trials “….should go far beyond efficacy…to include measures of harm as well as benefit and to integrate patient’s views on the quality of life with and without treatment, and to include economic consequences of the treatment alternatives.”

23. Cochrane Meta-analysis of Effect of Epidural Analgesia • Comparing Epidural to Narcotics • Previously meta-analyses showed a 10% increase in Cxion rate with epidural analgesia • Current Cochrane does not—why not? Is Cochrane wrong? • It is not the fault of the RCT as a methodology!! • It is the inclusion in the meta-analysis of studies that ought not to be there—or the studies need to be grouped or stratified according to their settings or approaches so one can know if the results apply to one’s own setting

24. Central Concepts in Applicability of EBM • Look at both the left and the right side of the equation • What about the “inadvertent” consequences of the approach or procedure addressed by the trial or what youare interested in compared to the big picture consequences for this and future pregnancies?

25. 4.3 hour increase with epidural Sharma only 1 hour increase with epidural

26. 1.4 hour increase with epidural Sharma only 19 min increase with epidural

27. 38% 52% Sharma only 33% epidural 15% control

28. 15% 7%

29. 27% 16% Increase in Perineal trauma as well Sharma only 9.1% epidural versus 3.6% control

30. 24% 6%

31. Why not an increase in cesarean as well?

32. All studies: mixed parity, various concentrations of agents both study arms and mostly IM narcotic 12-13% 10-14% 5% both arms Sharma: Dallas Parkland 12% base Cxion rate, low dose oxy augmentation, Randomization @4-5cms. Clark: Louisville, 70%>4 cms, high dose oxy, Loughan: London UK Randomization 3-4cms, Sharma!!!!

33. Klein Sensitivity Analysis: retaining only those studies that randomized early at < 4-5 cms

35. Wong CA, Scavone BM, Peaceman AM, McCarthy RJ, Sullivan JT, Diaz NT, et al. The risk of cesarean delivery with neuraxial analgesia given early versus late in labor. N Engl J Med 2005;352: 655-65 • Authors and NEJM editorialist claimed that early epidurals do not increase the rate of caesarean deliveries. • The study was not of early epidural analgesia, and the oxytocin augmentation rate of 75% at first analgesia makes for lack of generalisability. • The claim that women need not worry that early epidurals will lead to increased caesareans is false.

36. This trial was about two methods of helping women with pain in early labour. • In the so called epidural arm, an epidural catheter was placed. On first request for analgesia, women received intrathecal fentanyl, and in the narcotic arm, hydromorphone. • On second request, almost two thirds of women in both arms were in active labour, 4 cm or more dilated. • In the intrathecal "epidural" arm, they received low dose epidurals; in the narcotic arm, hydromophone.

37. This trial, as others that have contributed to the Cochrane meta-analysis showed no increase in caesareans in the presence of epidural analgesia, but does not acknowledge that most women were in active labour at time of second request or when they actually got an epidural-- when most will do well. • Wong et al, like Sharma et al, the other major contributors to the Cochrane meta-analysis showing no difference, have shown only that when women's pain in the latent phase is managed with intrathecal, narcotic, or other pharmacological or non-pharmacological means, an epidural in the active phase of labour does not increase the rate of caesarean section. • And neuraxial analgesia. Mmmmmmmmmmmmmm

38. Ohel from Israel (Am J Obs and Gyn 2006 vol 194) • Well conducted RCT of Epidural vs Narcotics • 449 nulliparous women at term randomized at less than 3 cms • Mean point of randomization 2.6 vs 4.6 cms for epidural vs narcotic • CS 13% vs 11% (LOW!!!!!!!!!!!!!) • But labor supported by nurse midwives fully—Obstetricians only as consultants • Clearly an intimate style of care • Again it is about environment—yours?

39. Latest Meta-analyses • Patient-requested Neuraxial Analgesia for Labor--Marucci et al Anesthesiology May 2007 • Review comes up with the same conclusions based on the same literature • New Cochrane meta-analysis same • All now state that early epidurals are not a problem

40. Epidural analgesia, while a superb technology, and the “best” form of pain relief has completely transformed normal birth--leading to a cascade of interventions. • 3 of 4 Canadian women receive one or more major procedures or interventions in labor (CIHI, 2004) and epidurals are a major contributing cause: Epidural Rate 45.4% Canada, 36.3% Vancouver and rising

41. Why don’t we acknowledge that Epidural Analgesia has changed the landscape? • Subversion by RCTs and EBM? • Cochrane reviews by • Anesthesiologists? • Nurse/Doctor’s comfort—we like it!! • Economics? • Existence of a dedicated anesthetic workforce that we created? • Not the fault of the anesthesia establishment!!!!! We asked for it • Women asked for it • (Think Twilight Sleep) • but we taught them to ask for it!

42. From EBM to Research designed to deliver answers that we want to receive!From Evidence-based decision-makingTo what Philip Hall has called: • “Decision Based EvidenceMaking”

43. Whose evidence? • Does the study setting apply to me in my setting? • Basic problems with RCTs • Results apply only for the conditions of the trial (“Murray Enkin’s first law”) • Are conditions my conditions? • Do the participating practitioners practice the way that I practice?

44. Collateral damage or Blowby (2) • Example: Canadian Post-Term trial of expectant management vs induction at 41 weeks • Outside rarified atmosphere of the RCT, thinking that placenta degenerates at 41 3/7th weeks unleashes a cascade of “side effects” NO! EFFECTS--resulting in increased not decreased cxion rates and consequences for next pregnancy: 8% vs 44% cxion rate for nulliparous women at BC Womens

45. Post-term trial: this and subsequent pregnancies, increase in: • induction, EFM, epidurals, instrumentation, perineal trauma, Cxions, sense of failure, parenting problems, postpartum DIC • Next pregnancy: placental previa and other problems of placentation, abruptions, ectopics, infertility, stillbirths

46. The Induction Cascade • Induction requires continuous electronic fetal monitoring because it is considered a “high risk” procedure. • This is because over-stimulation of the uterus can occur and that can lead to stress on the fetus. • Women receiving continuous electronic fetal monitoring are kept in bed almost all the time. • Immobility leads to abnormal progress of labor, which in turn leads to labour dysfunction

47. Induction Cascade 2 • Continuous electronic fetal monitoring leads to more cesarean sections, likely because of the immobility and because abnormalities that are seen on the monitoring tracings are often misinterpreted as “fetal distress,” and cesarean is the usual response. --Labors that are induced are more painful than labors that occur naturally. --Hence women are much more likely to receive an epidural analgesic than women in spontaneous labor.

48. Induction Cascade 3 • Epidural analgesia gives very effective pain relief—but “there is no free lunch!” --Epidural analgesia causes posterior pituitary gland to produce less natural oxytocin --Epidural analgesia will greatly prolong the first stage of labor on average by 3-4 hours

49. Induction Cascade 4 • If given very early in labor at less than 4 centimeters of cervical dilation (which is the case in most labors), epidural analgesia causes abnormal positions of the fetus, such as an extended neck rather than the usual flexed position. This leads to more back labors (posterior labors) and transverse or side positions. • A baby whose head is extended cannot rotate and cannot easily descend in the birth canal. • Epidural analgesia will increased the length of the second stage of labor by at least 30 minutes

50. Induction Cascade 5 • Epidural analgesia will lead to the inability of women to push effectively, thus leading to more use of synthetic oxytocin and need for assistance in the delivery by use of vacuum or forceps. --The use of these instruments in the presence of epidural analgesia, and even without, will lead to more perineal trau requiring stitching. --If given early in labor, epidural analgesia will increase the cesarean section rate by more than two times over women not receiving epidurals at all or only after 4-5 centimeters of cervical dilation.