Labetalol vs Nifedipine for Preeclampsia: How do they Affect Cerebral Perfusion Pressure?

BACKGROUND AND PURPOSE:

Women with preeclampsia have elevated cerebral perfusion pressure
Tolcher et al. (AJOG, 2020) compared cerebral perfusion pressure before and after IV labetalol vs oral nifedipine during severe hypertension in pregnancy

Prospective cohort study
Participants
- Between 24 and 42 weeks gestation | Severe hypertension
- Exclusion criteria: Active labor |Received other antihypertensive medication within 2 hours of initial cerebral perfusion pressure measurement
Exposures
- Labetalol group: 20 mg IV
- Nifedipine group: 10 mg oral
Study design
- Severe hypertension: SBP ≥160 and/or DBP ≥110
- Peripheral blood pressure and transcranial MCA Doppler studies obtained
  - Before medication administration
  - 30 minutes after medication administration
- Cerebral perfusion pressure can be measured with non-invasive transcranial Doppler
Multiple baseline data were obtained, including
- Maternal age | Parity | Race and ethnicity | BMI Gestational age | Pre-existing diabetes or hypertension | FGR | Magnesium sulfate
Primary outcome
- Change in cerebral perfusion pressure

16 women were enrolled | 8 women in each group
- No significant baseline characteristic differences between groups
There was a significantly greater decrease in the following 30 minutes after the administration of oral nifedipine vs IV labetalol for the following
- Systolic blood pressure (P = 0.003)
  - Intravenous labetalol: -9.8 mmHg
  - Oral nifedipine: -39 mmHg
- Mean arterial pressure (P = 0.02)
  - Intravenous labetalol: -7.1 mmHg
  - Oral nifedipine: -22.3 mmHg
- Cerebral perfusion pressure (P = 0.01)
  - Intravenous labetalol: -2.5 mmHg
  - Oral nifedipine: -27.7 mmHg
There was no statistically significant difference in
- Diastolic pressure (P = 0.15)
  - Intravenous labetalol: -12.9 mmHg
  - Oral nifedipine: -5.4 mmHg
- Change in middle cerebral artery velocity by transcranial Doppler (P = 0.64)
  - Intravenous labetalol: 0.07 cm/s
  - Oral nifedipine: 0.16 cm/s

Cerebral perfusion pressure was significantly decreased following a single dose of oral nifedipine vs IV labetalol in patients with severe hypertension in the setting of preeclampsia
The evidence suggests that this decrease is not due to a change in cerebral blood flow but rather a decrease in peripheral arterial blood pressure
The authors note that future research should include Doppler measurements of anterior and especially posterior cerebral arteries as “most neuropathology in the setting of preeclampsia occurs in the occipital region”

Tranexamic acid (TXA) is used to reduce blood loss and transfusion perioperatively
- Topical administration of TXA has been studied, but its safety and efficacy are still unclear
Teoh et al. (Annals of Surgery, 2020) performed a review to assess the effect of topical TXA on incidence of blood transfusion and mortality in adults undergoing surgery

Total 71 trials | Combined total of 7539 participants
- Orthopedic participants: 5450
- Nonorthopedic including gyn: 1909
Risk of bias assessment for all included studies
- Low: 20 studies
- Unclear: 26 studies
- High: 25 studies
Variation in dosing and route
- Dosage of topical TXA: 0.5 g to 3.0 g of TXA in 20 to 400mL of normal saline
- Application route: Wound irrigation and spraying | Gyn studies included applying a soaked sponge onto the operative site or wound irrigation
When compared to placebo, topical TXA significantly reduced
- Intraoperative blood loss: Mean difference (MD) -36.83 mL (95% CI, -54.77 to -18.88; P<0.001)
- Total blood loss: MD -319.55 mL (95% CI, -387.42 to -251.69; P<0.001)
- Incidence of blood transfusion: Odds ratio (OR) 0.30 (95% CI 0.26 to 0.34; P<0.001)
Topical TXA were associated with a shorter length of hospital stay
- MD -0.28 days (95% CI, -0.47 to -0.08; P = 0.006)
The following adverse events were not associated with topical TXA
- Mortality: P=0.39
- Pulmonary embolism: P=0.52
- DVT: P=0.79
- Myocardial infarction: P=0.73
- Stroke: P = 0.77

Topical TXA was associated with a decrease in intraoperative blood loss, total blood loss | Blood transfusion was reduced by 70%
TXA dose and route varied | However, previous studies did not find TXA effect to be dose dependent
Mortality was not affected
- However, authors note that larger numbers may be required To detect differences in mortality
- Mortality is at higher risk for confounding due to various comorbidities and other factors
No adverse effects related to the use of topical TXA were observed