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Hypertensive Pulmonary Edema
Sean Collins, MD, MSc
Associate Professor
Vanderbilt University 
Department of Emergency Medi...
Disclosures
• Consultant: Novartis, Cardiorentis, The 
Medicines Company, Medtronic
• Research Support: NIH, PCORI, Novart...
AHF and Elevated BP
Hypertensive Pulmonary Edema
Hypertensive Pulmonary Edema
Scenario
• 75 YO F with h/o HTN and HF with SOB
• BP- 180/100 P-80 RR-24  Satn- 84%
• Moderate respiratory distress
• Diff...
Q: Initial stabilization for this patient
may include which of the following?
• a) Non invasive ventilation
• b) Sublingua...
ESC Guidelines for Pulm Edema
McMurray et al. EHJ 2012; 33
Treat 
then 
Test
Collins et al. Ann Emerg Med 2008;51:45-57.
Q: All of the following are true about
Non-invasive ventilation except:
• a) It improves acidosis
• b) It improves work of...
Non-invasive Ventilation - A
Therapy
• Consider if acute respiratory distress
– CPAP: continuous positive airway pressure ...
Collins S. Ann Emerg Med 2006;48:260-69
Prevents Intubation in ED Patients
Prevents Intubation in
Hospitalized HF Patients
Masip JAMA 2005;294;24
  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 ...
Gray et al. NEJM 2008;359:142-51.
Gray et al. NEJM 2008;359:142-51.
NIV Improved Dyspnea
NIV improves acidosis
Gray et al. NEJM 2008;359:142-51.
Gray A, Goodacre S, Newby DE et al., for 3 CPO trialists
• No difference in 
tracheal intubation 
(overall rate 2.8%)
• No...
• Q: T/F: High-dose IV Nitrates have been 
used safely in the prehospital and ED 
environment for AHF
• A) True
• B) False
High-Dose Ntg for
Hypertensive Pulm Edema
• Entry criteria
– Systolic BP  160 mmHg or MAP  120
– Failed initial tx: O2, ...
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...
• 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
– M...
How Are Nitrates Usually Dosed?
• Isosorbide dinitrate (ISDN)
– Widely used outside the US
– Typical range: 1-4 mg/hr
• In...
ESC Guidelines
McMurray et al. EHJ 2012; 33
2 mg bolus every 3 minutes! 
3 mg bolus every 5 minutes! 
PRONTO- IV Calcium Channel Blocker
• Open label, randomized 1:1 (CLV vs. SOC)
• Acute Heart Failure (AHF) with SBP ≥ 160 m...
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
Clevi...
Mean Change in BP
Peacock Am Heart J 2014 Apr; 167(4):529-36
SECONDARY ENDPOINT
VAS score over time (Confirmed AHF)
VASscore,mm(mean±SE)
Time From Initiation of Study Medication (hrs)...
Safety of BP Reduction
Safety
    CLV
    N = 51
   SOC
   N = 53
SAE 12  (24%) 10  (19%)
30-day  mortality  3  (%) 2  (%)...
Alexander Am J Emer Med  2015 Feb 133-41
8 on nitrates, 20 on nesiritide
• Hydralazine- 1 study with limitations1
• Enalaprilat - 2 studies- 34 total AHF 
patients1
• “Evidence Free Zone”
Alexand...
Collins et al, Acad Em Med Jan 2015
Summary: Hypertensive Pulm Edema
• AHF + Significant BP elevation
• Early and aggressive treatment improves 
symptoms- out...
Thank You
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Hypertensive acute pulmonary edema

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Hypertensive acute pulmonary edema

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Hypertensive acute pulmonary edema

  1. 1. Hypertensive Pulmonary Edema Sean Collins, MD, MSc Associate Professor Vanderbilt University  Department of Emergency Medicine
  2. 2. Disclosures • Consultant: Novartis, Cardiorentis, The  Medicines Company, Medtronic • Research Support: NIH, PCORI, Novartis,  Cardiorentis, Trinity
  3. 3. AHF and Elevated BP
  4. 4. Hypertensive Pulmonary Edema
  5. 5. Hypertensive Pulmonary Edema
  6. 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. 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. 8. ESC Guidelines for Pulm Edema McMurray et al. EHJ 2012; 33
  9. 9. Treat  then  Test Collins et al. Ann Emerg Med 2008;51:45-57.
  10. 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. 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. 12. Collins S. Ann Emerg Med 2006;48:260-69 Prevents Intubation in ED Patients
  13. 13. Prevents Intubation in Hospitalized HF Patients Masip JAMA 2005;294;24
  14. 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. 15. Gray et al. NEJM 2008;359:142-51.
  16. 16. Gray et al. NEJM 2008;359:142-51. NIV Improved Dyspnea
  17. 17. NIV improves acidosis Gray et al. NEJM 2008;359:142-51.
  18. 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. 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. 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. 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. 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. 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. 24. ESC Guidelines McMurray et al. EHJ 2012; 33 2 mg bolus every 3 minutes!  3 mg bolus every 5 minutes! 
  25. 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. 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. 27. Mean Change in BP Peacock Am Heart J 2014 Apr; 167(4):529-36
  28. 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. 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. 30. Alexander Am J Emer Med  2015 Feb 133-41 8 on nitrates, 20 on nesiritide
  31. 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. 32. Collins et al, Acad Em Med Jan 2015
  33. 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. 34. Thank You

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