Hypertensive acute pulmonary edema

1. Hypertensive Pulmonary Edema
Sean Collins, MD, MSc
Associate Professor
Vanderbilt University
Department of Emergency Medicine

2. Disclosures
• Consultant: Novartis, Cardiorentis, The
Medicines Company, Medtronic
• Research Support: NIH, PCORI, Novartis,
Cardiorentis, Trinity

3. AHF and Elevated BP

4. Hypertensive Pulmonary Edema

5. Hypertensive Pulmonary Edema

6. Scenario
• 75 YO F with h/o HTN and HF with SOB
• BP- 180/100 P-80 RR-24 Satn- 84%
• Moderate respiratory distress
• Diffuse rales; +JVD, trace leg edema
• CXR = pulmonary edema; U/S = comet tails
• Treatment?

7. Q: Initial stabilization for this patient
may include which of the following?
• a) Non invasive ventilation
• b) Sublingual/IV nitrates
• c) Dobutamine
• d) 1) and 2)
• e) All of the above

8. ESC Guidelines for Pulm Edema
McMurray et al. EHJ 2012; 33

9. Treat
then
Test
Collins et al. Ann Emerg Med 2008;51:45-57.

10. Q: All of the following are true about
Non-invasive ventilation except:
• a) It improves acidosis
• b) It improves work of breathing
• c) It decreases overall mortality
• d) It is relatively easy to apply

11. Non-invasive Ventilation - A
Therapy
• Consider if acute respiratory distress
– CPAP: continuous positive airway pressure 1,2
• Reduction in need for ETI by 26 %
• Trend towards ↑ survival
– BiPAP: bilevel positive airway pressure 3,4,5
• ↓ time to symptom resolution (30 vs. 105 min)
• ↓ intubation rate (~ 23 %)
1 Berstein et al. NEJM 1991;325.
2 Pang et al. Chest 1998;114.
3 Masip et al. Lancet 2000;356
4 Levitt MA. J Emerg Med 2001;21.
5 Nava et al. Am J Resp Crit Care Med 2003;168

12. Collins S. Ann Emerg Med 2006;48:260-69
Prevents Intubation in ED Patients

13. Prevents Intubation in
Hospitalized HF Patients
Masip JAMA 2005;294;24

14. 12L face mask
5-10 cm water
Insp 8-20/exp 4-10
• Standard O2(n=367)
• CPAP (n=346)
• NIPPV (n=356)
Gray A, Goodacre S, Newby DE et al., for 3 CPO trialists
• Multicenter, prospective, open, randomized (1:1:1)
• Primary endpoint SOC v NIV d7 mortality
• Primary endpoint CPAP v NIPPV d7 mort and ETT
• Prespecified secondary endpoints: dyspnea, hospital
LOS, 30d mortality, ICU admission

15. Gray et al. NEJM 2008;359:142-51.

16. Gray et al. NEJM 2008;359:142-51.
NIV Improved Dyspnea

17. NIV improves acidosis
Gray et al. NEJM 2008;359:142-51.

18. Gray A, Goodacre S, Newby DE et al., for 3 CPO trialists
• No difference in
tracheal intubation
(overall rate 2.8%)
• No increase in MI in
NIV
• No mortality benefit
• Earlier improvement
of dyspnea
Take home points:
-May not save lives
-Improves symptoms and resp
distress
-Provides time for other therapies
to be started

19. • Q: T/F: High-dose IV Nitrates have been
used safely in the prehospital and ED
environment for AHF
• A) True
• B) False

20. High-Dose Ntg for
Hypertensive Pulm Edema
• Entry criteria
– Systolic BP  160 mmHg or MAP  120
– Failed initial tx: O2, SL Ntg x 3, furosemide
• Protocol
– 2 mg IV Ntg bolus, titration and repeat q3 mins
– May repeat x 10
Levy Ann Emerg Med 2007 Aug; 50(2)
20,000 μgm
30 mins

21. HD Ntg Controls P value
Mech vent 20.7 % 46.7 % 0.023
ICU admit 37.9 % 80.0 % <0.001
Hosp LOS
(days)
4.1  3.4 6.2  7.3 0.171
NSTEMI 17.2 % 28.9 % 0.254
Low BP 3.4 % 0 % 0.210
Levy Ann Emerg Med 2007 Aug; 50(2)
High Dose Ntg for
Hypertensive Pulm Edema

22. • IV ISDN 3 mg q 5 min (n = 52) vs. IV
furosemide (N = 52) 80 mg q 15 min
– Mean dose ISDN = 11.4 (± 6.8) mg
– Mean dose furosemide = 200 (± 65) mg
Cotter et al. Lancet 1998:351:389-3.

23. How Are Nitrates Usually Dosed?
• Isosorbide dinitrate (ISDN)
– Widely used outside the US
– Typical range: 1-4 mg/hr
• Increase by 1 mg/hr every 10 min as needed
• Nitroglycerin (NTG)
– Nitrate of choice in US
– Typical range: 10-20 mcg/min
• Increase 5 mcg/min every 5 min as needed
1 Mebazza et al. Crit Care Med 2008; 36:S129–S139.
2 Chatti et al. Heart Fail Rev 2007;12:113-7.
3 Kirk et al. Crit Pathways in Cardiol 2008;7:103-10.

24. ESC Guidelines
McMurray et al. EHJ 2012; 33
2 mg bolus every 3 minutes!
3 mg bolus every 5 minutes!

25. PRONTO- IV Calcium Channel Blocker
• Open label, randomized 1:1 (CLV vs. SOC)
• Acute Heart Failure (AHF) with SBP ≥ 160 mmHg
• Primary objective:
– To evaluate the safety and efficacy of clevidipine vs.
SOC IV anti-HTNs in ED AHF with hypertension
Peacock Am Heart J 2014 Apr; 167(4):529-36

26. Choice of Standard Therapy
Drug Name (n),
[dose unit] μg /min or mg/hr1
min/max
μg/min or mg/hr
Total dose
μg or mg1
Clevidipine (n=51) [mg] 6.0 (4.0, 8.0) 1.0/32.0 4.0 (1.9, 6.3)
IV SOC Meds (n=54)
Nitroglycerin (30) [μg] 31.7 (13.3, 50) 3.3/200 930 (400, 1560)
Nicardipine (16) [mg] 6.3 (5.0, 8.2) 1.0/10.0 3.15 (2.5, 4.4)
ISDN (4) [mg] 90.5 (1.0, 360) 1.0/540 4.75 (0.5, 39.0)
Hydralazine (1) [mg] --- --- 20 bolus
Diltiazem (1) [mg] 10 (na) 10/10 5.0 (na)
Nitroprusside (1) [μg] 13.3 (na) 13.3/13.3 400 (na)
Peacock Am Heart J 2014 Apr; 167(4):529-36

27. Mean Change in BP
Peacock Am Heart J 2014 Apr; 167(4):529-36

28. SECONDARY ENDPOINT
VAS score over time (Confirmed AHF)
VASscore,mm(mean±SE)
Time From Initiation of Study Medication (hrs)
*
** ***
*∆ = -10.4 mm, p = 0.017
** ∆ = -11.7 mm, p = 0.020
*** ∆ = -14.0 mm, p = 0.015
p = 0.037 for treatment x time effect
Peacock Am Heart J 2014 Apr; 167(4):529-36

29. Safety of BP Reduction
Safety
CLV
N = 51
SOC
N = 53
SAE 12 (24%) 10 (19%)
30-day mortality 3 (%) 2 (%)
Patients with drug–related TEAEs 5 (10%) 7 (13%)
Cardiac 1 (2%) 0 (0%)
Respiratory 0 (0%) 0 (0%)
Gastrointestinal 2 (4%) 0 (0%)
Renal 0 (0%) 0 (0%)
CNS (all headache) 1 (2%) 7 (13%)*
Vascular 1 (2%) 0 (0%)
p > 0.05 CLV vs. SOC
*p > 0.05 CLV vs. SOC

30. Alexander Am J Emer Med 2015 Feb 133-41
8 on nitrates, 20 on nesiritide

31. • Hydralazine- 1 study with limitations1
• Enalaprilat - 2 studies- 34 total AHF
patients1
• “Evidence Free Zone”
Alexander Am J Emer Med 2015 Feb 133-41

32. Collins et al, Acad Em Med Jan 2015

33. Summary: Hypertensive Pulm Edema
• AHF + Significant BP elevation
• Early and aggressive treatment improves
symptoms- outcomes??
• NIV, Nitrates/vasodilators, Diuretics
• Rapid improvement if hemodynamics
addressed early

34. Thank You