Tabassum Firoz, MD FRCPC

University of British Columbia, Canada PRE-EMPT [Pre-eclampsia/Eclampsia Evaluation, Monitoring and Treatment]

1. Definition of severe hypertension

2. Severe hypertension and maternal morbidity 3. Choice of antihypertensive therapy

2 RCTs (133 women) show that expectant care of early severe pre-eclampsia was associated with a mean pregnancy prolongation of 2.0 wk [1.4, 2.6] 1
A 2009 systematic review found that expectant care of severe preeclampsia <34 wk (39 cohorts, 4,650 women) was associated with pregnancy prolongation of 7-14 days2

___________________________________________________________
1Obstet Gynecol

1990;76:1070-5; AJOG 1994;171:818-822 2Hypertens Pregnancy 2009;28(312-47.

MAP of 107mmHg = 140/90mmHg

MAP of 140mmHg = 180/120mmHg

Seems likely that pregnancy shifts the curve to the LEFT and Possibly also causes increased vascular PERMEABILITY

Guideline

sBP definition

dBP definition
110 mmHg

Canada: Society of 160 mmHg Obstetricians & Gynecologists of Canada (2008) UK: NICE The Management of Hypertensive Disorders During Pregnancy (2010) US: ASH Position Article: Hypertension in Pregnancy (2008) Australasia: SOMANZ Guidelines for the Management of Hypertensive Disorders of Pregnancy (2008) 160 mmHg

110 mmHg

160 mmHg

110 mmHg

170 mmHg

110 mmHg

 In

a retrospective case series of 28 women with stroke, right before their stroke1 o96% had a sBP of 160mmHg o13% had a dBP of 110mmHg
2005;105:246-54

1Obstet Gynecol

The single major

failing in clinical care in the current triennium was, again, inadequate treatment of hypertension with subsequent intracranial hemorrhage

Saving Mothers Lives 2006-2008, published March 2011

Women with severe hypertension should receive treatment with antihypertensive therapy

Very low quality evidence Strong Recommendation

WHO Recommendations for Prevention and Treatment of Pre-eclampsia and Eclampsia 2011

The choice and route of administration of an antihypertensive drug for severe hypertension during pregnancy, in preference to others, should be based primarily on the prescribing clinicians experience with that particular drug, its cost and local availability.

Very-low-quality evidence Weak recommendation

 2010:

NICE guidelines provide most up-to-date summary (30 trials 3,446 women)1 Cochrane Database of Systematic Reviews (24 trials, 2,959 women) 2 BMJ (21 trials, 1,085 women) 3

2009:

2003:

Two approaches differed in regards to inclusion of quasirandomised trials, use of RR and RD (risk difference)

One antihypertensive therapy vs. another, OR, hydralazine vs. any other antihypertensive
1http://guidance.nice.org.uk/CG/Wave15/10 2DOI: 10.1002/14651858.CD001449.pub2 3BMJ 2003;327:955-60

Persistent severe hypertension

Maternal hypotension

Adverse FHR effects N=18 trials RR 1.61 [1.03, 2.56] Significant heterogeneity isolated to hydralazine vs. LB group Adverse FHR effects were variably defined, mostly by inspection, vague definitions Low 1-min Apgars RR 2.70 [1.27, 5.88] Consistent between trials No difference in 5-min Apgars Bradycardia RD -0.24 [-0.42, -0.06]; All hydralazine vs. LB trials N=3 trials

N=3 trials

Nifedipine compared favourably with parenteral hydralazine with no differences seen in BP control or maternal or perinatal outcomes
The incidence of maternal hypotension in the nifedipine capsule arms of these trials was low (1/102, 3 trials), but hypotension was more common in both arms of a nifedipine 10mg capsule vs. 10mg PA tablet trial
o

11/31 in the capsule arm vs. 3/33 in the tablet arm with a relative difference of 0.26 [95% CI 0.07, 0.46]

**Unpublished data

Concerns have been raised about the safety of nifedipine capsules outside of pregnancy

Case reports in pregnancy describe the temporal association between nifedipine use and either maternal hypotension or neuromuscular blockade
However, risk of NM blockade has been estimated to be <1%, based on a single centre controlled study and synthesis of RCTs1

1AJOG 2005;193:153-63

Essential medicines are defined by the World Health Organization as drugs that satisfy the health care needs of the majority of the population
Essential Medicines List serve as an advocacy tool Inclusion on an EML does not guarantee a nations access to a medication, rather, it supports the argument that the medication should be routinely available.

Lalani et al. Submitted to BJOG 2012

Lalani et al. Submitted to BJOG 2012

There is consensus that severe hypertension (BP of 160170/110) should be treated The emphasis is on importance of treatment, rather than a specific antihypertensive Hypotension can occur with any agent BP goal in a hypertensive urgency should be achieved as outside pregnancy slowly

Most studied antihypertensive agents are labetalol (IV), hydralazine (IV), and nifedipine (po capsules) There are no definitive differences but hydralazine is not clearly the drug of FIRST choice Oral antihypertensive agents may be a reasonable choice in the facility setting Essential Medicines Lists have at least one option available for the treatment of severe hypertension